It is paradoxical that this book on ventricular/vascular coupling will occupy space in medical libraries alongside clinical texts on hypertension, cardiac failure, and ischemic heart disease. Paradoxical, because the approaches described... more
It is paradoxical that this book on ventricular/vascular coupling will occupy space in medical libraries alongside clinical texts on hypertension, cardiac failure, and ischemic heart disease. Paradoxical, because the approaches described here are rarely if ever addressed in these clinical texts, even though they are of paramount relevance and importance. Neglect of these approaches is all the more surprising when one considers that hypertension, cardiac failure, and ischemic heart disease are among the most common serious diseases handled regularly by practicing physicians.
Research Interests:
Research Interests: Cardiology, Drug interactions, Medicine, Platelet, Dogs, and 15 moreInternal Medicine, Animals, Male, Recurrence, Clinical Sciences, Coronary heart disease, Public health systems and services research, Circulation, Combination drug therapy, Streptokinase, Plasminogen Activator, epoprostenol, Prostacyclin, Platelet Aggregation Inhibitors, and Cardiovascular medicine and haematology
Research Interests:
Research Interests: Cardiology, Medicine, Dogs, Internal Medicine, Cardiovascular Pharmacology, and 12 moreAnimals, Male, Coronary heart disease, Blood Flow, Thrombosis, Coronary Circulation, Tissue Plasminogen Activator, epoprostenol, Prostacyclin, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences, and Thrombus
To determine the effect of dietary fish oil supplementation on myocardial dysfunction following ischemia-reperfusion, independent of plasma and blood cells, Sprague-Dawley rats were fed fish oil-rich nonpurified diet or butter-enriched... more
To determine the effect of dietary fish oil supplementation on myocardial dysfunction following ischemia-reperfusion, independent of plasma and blood cells, Sprague-Dawley rats were fed fish oil-rich nonpurified diet or butter-enriched diet for 5 d. Myocardial content of long-chain and (n-3) polyunsaturated fatty acids was greater in the fish oil-fed rats (P < 0.01), whereas (n-6) fatty acid content was lower compared with controls (P < 0.01). Platelet aggregation in fish oil-fed rats was also inhibited. Hearts from all rats were subjected to 15 min of global ischemia and 10 min of reperfusion. In hearts of control rats, ischemia-reperfusion resulted in a marked decrease in force of cardiac contraction, increase in coronary perfusion pressure, appearance of ventricular arrhythmias and release of creatine kinase and thromboxane B2 in the coronary effluent. Dietary fish oil supplementation attenuated myocardial dysfunction induced by ischemia-reperfusion, as indicated by smaller change in force of cardiac contraction (-77% vs. -89%, P < 0.05) and coronary perfusion pressure (+37% vs. +71%, P < 0.001). Concomitantly, release of creatine kinase as well as thromboxane B2 in coronary effluent was lower (P < 0.01). Ventricular arrhythmias occurred less frequently in hearts from fish oil-fed rats. Thus, short-term dietary fish oil supplementation attenuates myocardial dysfunction caused by ischemia-reperfusion by a direct effect on the heart independent of blood and plasma components.
Research Interests: Biology, Medicine, Animal Production, Internal Medicine, Ischemia, and 15 moreAnimals, Male, Heart rate, Heart, Fish Oil, Creatine Kinase, Lipid peroxidation, Cardiac Arrhythmias, Analysis of Variance, Fatty Acid, Food Sciences, Coronary Circulation, Blood cells, Malondialdehyde, and Medical and Health Sciences
Research Interests:
The coronary hemodynamic effects of intracoronary administration of a fibrin(ogen)-derived pentapeptide, Ala-Arg-Pro-Ala-Lys (peptide 6A), were evaluated in open-chest anesthetized dogs. With administration of peptide 6A (2.5-30 mumol),... more
The coronary hemodynamic effects of intracoronary administration of a fibrin(ogen)-derived pentapeptide, Ala-Arg-Pro-Ala-Lys (peptide 6A), were evaluated in open-chest anesthetized dogs. With administration of peptide 6A (2.5-30 mumol), coronary blood flow increased and coronary vascular resistance decreased promptly in a dose-related manner. Increase in coronary blood flow was independent of any change in indexes of myocardial O2 demand, indicating the peptide 6A exerts direct effects on coronary arterial tone. Systemic arterial and left ventricular end-diastolic pressures remained unchanged with smaller doses but decreased when higher doses of peptide 6A (greater than or equal to 20 mumol) were administered. Plasma concentrations of 6-ketoprostaglandin F1 alpha, stable hydrolysis product of prostacyclin, increased in coronary sinus blood samples in conjunction with increase in coronary blood flow. Administration of indomethacin (5 mg/kg iv) inhibited peptide 6A-induced release of ...
Research Interests:
The ascending aortic pressure wave in kangaroos is quite different from that seen in other experimental animals and in humans, despite an ascending aortic flow wave that is virtually identical. The diastolic pressure surge in the... more
The ascending aortic pressure wave in kangaroos is quite different from that seen in other experimental animals and in humans, despite an ascending aortic flow wave that is virtually identical. The diastolic pressure surge in the ascending aortic pressure wave of kangaroos is very prominent--so much so that peak diastolic pressure is often greater than peak systolic pressure, with the pressure wave resembling that recorded in humans during intra-aortic balloon counterpulsation. Ascending aortic impedance patterns in kangaroos indicate the presence of a single functionally discrete reflecting site in the peripheral circulation, with high reflection coefficient. All findings--of pulse contour and impedance patterns--are explicable on the basis of arterial anatomy and body shape. Wave reflection from the distant, large, and vascular lower body appears to dominate the effects of wave reflection from the short, small, and less vascular head and forelimb system.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Scanning Electron Microscopy, Medicine, Dogs, Internal Medicine, Platelet aggregation, and 15 moreHemodynamics, Female, Animals, Male, Heart, Artery, Public health systems and services research, Blood Flow, Fissipedia, Recombinant Proteins, Thrombolytic Therapy, Plasminogen Activator, The American, Thrombolysis, and Cardiovascular medicine and haematology
To determine the effect of dietary fish oil supplementation on myocardial dysfunction following ischemia-reperfusion, independent of plasma and blood cells, Sprague-Dawley rats were fed fish oil-rich nonpu- rified diet or butter-enriched... more
To determine the effect of dietary fish oil supplementation on myocardial dysfunction following ischemia-reperfusion, independent of plasma and blood cells, Sprague-Dawley rats were fed fish oil-rich nonpu- rified diet or butter-enriched diet for 5 d. Myocardial content of long-chain and (n-3) polyunsaturated fatty acids was greater in the fish oil-fed rats (P < 0.01), whereas (n-6) fatty acid content was lower compared with controls (P < 0.01). Platelet aggregation in fish oil-fed rats was also inhibited. Hearts from all rats were subjected to 15 min of global ischemia and 10 min of reperfusion. In hearts of control rats, ischemia-reper fusion resulted in a marked decrease in force of cardiac contraction, increase in coronary perfusion pressure, ap pearance of ventricular arrhythmias and release of creatine kinase and thromboxane 82 in the coronary effluent. Dietary fish oil supplementation attenuated my ocardial dysfunction induced by ischemia-reperfusion, as indicated by sm...
Research Interests:
Intravenous administration of thrombin inhibitors, such as hirudin, has been shown to decrease the frequency of coronary artery reocclusion after thrombolysis. However, recent findings in large clinical trials in patients with unstable... more
Intravenous administration of thrombin inhibitors, such as hirudin, has been shown to decrease the frequency of coronary artery reocclusion after thrombolysis. However, recent findings in large clinical trials in patients with unstable angina and myocardial infarction have failed to demonstrate a sustained antithrombotic effect after cessation of drug treatment. These findings indicate a need for a prolonged antithrombotic regimen, preferably an orally active thrombin inhibitor. To test the hypothesis that a regimen consisting of oral thrombin inhibitor will delay or prevent the formation of occlusive clot, anesthetized dogs were given saline (n = 9) or a single dose of a novel active site low-molecular-weight thrombin inhibitor melagatran by nasogastric tube (1.5 mg/kg, n = 6; 2.5 mg/kg, n = 6), and 15 min later, a potent thrombogenic stimulus in the form of anodal current (100 microA) was applied to the intimal surface of the narrowed left anterior descending coronary artery (LAD). All saline-treated dogs developed stable thrombus, indicated by zero flow at 34 +/- 7 min after initiation of direct current. On the other hand, one of the six dogs given high-dose melagatran did not develop thrombotic occlusion of the LAD during the entire 4 h of observation. Mean time to occlusive thrombus formation in 11 other dogs was prolonged 4-5 times as compared with that in the saline-treated dogs (p &lt; 0.001). Spontaneous thrombolysis was observed in three of 11 dogs after initial clot formation. Overall, the coronary artery was patent for 68% (low dose) and 75% (high dose) of the observation period in melagatran-treated dogs (vs. 14% of observation period in saline-treated dogs). Peak plasma concentration was 0.87 +/- 0.22 microM in dogs given low-dose and 1.38 +/- 0.30 microM in dogs given high-dose melagatran. The activated partial thromboplastin time (aPTT) increased 1.5-fold at peak plasma concentration of melagatran. These observations imply (a) thrombin generation plays a critical role in thrombus formation in narrowed coronary arteries, (b) oral melagatran prevents or delays thrombus formation, whereas the aPTT is only modestly prolonged, and (c) the thrombus formed in the presence of melagatran is prone to spontaneous lysis in this canine model of coronary thrombosis.
Research Interests: Scanning Electron Microscopy, Medicine, Dogs, Fibrinogen, Thrombin, and 11 moreCardiovascular Pharmacology, Animals, Saline, Antithrombotic, Glycine, Arterial Occlusive Diseases, Thrombolysis, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences, Thrombus, and Electric stimulation
Peptide 6A, a degradation of B beta chain of fibrinogen, is known to increase coronary and femoral blood flow. In this study, we examined the effects of peptide 32, an analogue of peptide 6A on coronary blood flow in anesthetized dogs.... more
Peptide 6A, a degradation of B beta chain of fibrinogen, is known to increase coronary and femoral blood flow. In this study, we examined the effects of peptide 32, an analogue of peptide 6A on coronary blood flow in anesthetized dogs. Intracoronary administration of equimolar amounts of peptide 32 and peptide 6A showed a greater (p &lt; 0.05) increase in blood flow with peptide 32. Intravenous administration of peptide 32 also resulted in greater and longer-lasting increase in coronary blood flow. The greater blood flow enhancing effect of peptide 32 than that of peptide 6A may relate to absence of its degradation by angiotensin converting enzyme.
Research Interests: Chemistry, Mast Cells, Medicine, Dogs, Blood Pressure, and 12 moreCardiovascular Pharmacology, Animals, Peptide, Lysine, Rats, Blood Flow, Coronary Circulation, Amino Acid Sequence, Vascular Resistance, Molecular Sequence Data, Cardiovascular medicine and haematology, and Pharmacology and pharmaceutical sciences
ABSTRACT
Research Interests:
Research Interests: Cardiology, Medicine, Dogs, Internal Medicine, Cardiovascular Pharmacology, and 13 moreAnimals, Male, Coronary heart disease, Blood Flow, Thrombosis, Coronary Circulation, Coronary Artery Disease, Tissue Plasminogen Activator, epoprostenol, Prostacyclin, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences, and Thrombus
Release of superoxide radicals during the early phase of coronary reperfusion may result in degradation of endothelium-derived relaxing factor (EDRF), extension of myocardial injury, precipitation of arrhythmias, and stimulation of... more
Release of superoxide radicals during the early phase of coronary reperfusion may result in degradation of endothelium-derived relaxing factor (EDRF), extension of myocardial injury, precipitation of arrhythmias, and stimulation of platelet aggregation. These factors may relate to the occurrence of ventricular fibrillation during reperfusion and coronary reocclusion following initial thrombolysis. This study was designed to examine the effects of concomitant administration of superoxide radical scavenger superoxide dismutase (SOD) with tissue plasminogen activator (tPA) compared to tPA alone (without SOD) in acute coronary thrombosis in anesthetized dogs. Dogs with a stable electrically induced coronary thrombus were randomly given intravenously tPA (0.75 mg/kg) alone or SOD bolus (2 mg/kg) followed by SOD (4 mg/kg) + tPA (0.75 mg/kg) over 20 min. tPA alone restored coronary blood flow in six of nine dogs (reperfusion rate of 67%) with time to reflow of 18.5 +/- 6.7 (mean +/- SD) min. Coronary reocclusion occurred spontaneously in four of six dogs with initial reperfusion (reocclusion rate of 67%). In contrast, SOD + tPA restored coronary blood flow in 9 of 12 dogs (reperfusion rate of 75%, not significant vs. tPA alone) with time to reflow of 11.3 +/- 4.8 min and coronary reocclusion occurred in only 3 of 9 dogs with reperfusion (reocclusion rate of 33%, not significant vs. tPA alone). Reperfusion arrhythmias were more frequent in dogs who received tPA alone compared to those who received SOD in addition to tPA (mean Holter-monitored PVC count of 730 vs. 12 beats/h, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Research Interests: Cardiology, Medicine, Dogs, Internal Medicine, Platelet aggregation, and 15 moreHemodynamics, Cardiovascular Pharmacology, Female, Animals, Heart, Acetylcholine, Superoxide Dismutase, Cardiac Arrhythmias, Coronary heart disease, Arrhythmia, Recombinant Proteins, Plasminogen Activator, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences, and Coronary Vessels
Diminished coronary flow reserve and myocardial dysfunction following coronary artery occlusion and reperfusion have been attributed to neutrophil infiltration into the reperfused regions. Release of free radicals and elastase during... more
Diminished coronary flow reserve and myocardial dysfunction following coronary artery occlusion and reperfusion have been attributed to neutrophil infiltration into the reperfused regions. Release of free radicals and elastase during reperfusion may also contribute to ischaemia-reperfusion induced changes. The aim of this study was to determine the effect of an elastase inhibitor on reperfusion induced attenuated coronary flow reserve and myocardial dysfunction. Anaesthetised dogs were subjected to 1 h of left anterior descending coronary artery occlusion and 2 h of reperfusion. Ten minutes before reperfusion, dogs were randomly given saline or the neutrophil elastase inhibitor ICI 200,880 (10 mg.kg-1) and treatment was continued for the next 70 min. While the regional myocardial shortening fraction and coronary blood flow responses to acetylcholine and glyceryl trinitrate were attenuated following coronary reperfusion in saline treated dogs, similar reductions were not observed in the ICI 200,880 treated dogs (p &lt; 0.01). Histopathology showed myocardial injury and extensive neutrophil infiltration in the reperfused regions in saline treated animals. In contrast, neutrophil infiltration was minimal in the ICI 200,880 treated dogs, in spite of myocardial injury. Myeloperoxidase, an index of neutrophil infiltration, was increased (p &lt; 0.02 v control regions) in the reperfused regions in saline treated dogs, but not in the ICI 200,880 treated dogs. Flow cytometry also showed diminished neutrophil infiltration and oxidative burst in reperfused myocardium of ICI 200,880 treated (v saline treated) dogs. The elastase inhibitor ICI 200,880 protects against ischaemia-reperfusion induced attenuated coronary flow reserve and myocardial dysfunction, and this protective effect is associated with decreased neutrophil infiltration into the reperfused regions.
Research Interests: Cardiology, Cardiovascular, Medicine, Dogs, Internal Medicine, and 13 moreAnimals, Acetylcholine, Neutrophils, Myocardium, Coronary Circulation, Coronary Artery Disease, Nitroglycerin, Coronary Flow Reserve, Constriction, Coronary artery, Random Allocation, Cardiovascular medicine and haematology, and Coronary Vessels
ABSTRACT
Research Interests:
Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic... more
Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man.
Research Interests: Cardiology, Cardiovascular, Medicine, Electrocardiography, Humans, and 15 moreInternal Medicine, Left Ventricular Assist Device, Blood Pressure, Male, Heart rate, Cardiac Catheterization, Middle Aged, Adult, Angina pectoris, Aorta, Heart Ventricles, Blood Flow Velocity, Aortic pressure, Left Ventricular, and Cardiovascular medicine and haematology
Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence,... more
Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence, aspirin and thrombin inhibitors are often used in patients with acute myocardial infarction. This study was designed to examine the modulation of coronary artery reocclusion by a novel low molecular weight direct thrombin inhibitor inogatran with or without aspirin. 22 dogs with electrically-induced occlusive intracoronary thrombus were treated with saline (n = 7, group A), or high dose inogatran (0.25 mg/kg bolus followed by 0.6 mg/kg per h for 2 h, n = 5, group B), or low dose inogatran (0.125 mg/kg bolus followed by 0.3 mg/kg per h for 2 h, n = 5, group C), or aspirin+low dose inogatran (n = 5, Group D). Recombinant tissue-plasminogen activator (rt-PA) was infused for 20 min starting 2 min after the bolus in all dogs. Coronary artery blood flow was monitored for 120 min after rt-PA administration. Reperfusion rates were similar in all groups, but the time to reperfusion was shortest in group B dogs (18 +/- 2 min vs. 32 +/- 7 min in group A dogs, P &lt; 0.05). Reocclusion rates were 80%, 0%, 50%, and 60% in groups A, B, C, and D dogs, respectively. The restored blood flow persisted for 19 +/- 10, &gt; 120 min, 71 +/- 30 and 54 +/- 26 min in groups A, B, C, and D dogs, respectively. At the end of rt-PA infusion, prothrombin time (PT) and activated partial thromboplastin time (APTT) were increased 1.3-2 times the control value, and the changes in PT and APTT were similar in all groups. Thrombin generation and activity, assessed by rise in thrombin-antithrombin complex and fibrinopeptide A levels, and decrease in fibrinogen levels were most marked in group A dogs, and less so in group B, C and D dogs. These data show that high dose of direct thrombin inhibitor inogatran shortens time to reflow and abolishes coronary artery reocclusion. However, aspirin does not potentiate the effect of suboptimal doses of inogatran.
Research Interests: Cardiology, Cardiovascular, Medicine, Dogs, Thrombin, and 14 moreFemale, Animals, Male, Anesthesia, Aspirin, Recurrence, Combination drug therapy, Coronary Circulation, Tissue Plasminogen Activator, Recombinant Proteins, Thrombolytic Therapy, Thrombolysis, Drug synergism, and Cardiovascular medicine and haematology
The coronary artery produces large amounts of prostacyclin (PGI2) and a small amount of thromboxane A2 (TXA2); this high PGI2/TXA2 ratio contributes to the antithrombotic properties of the coronary artery. This study was designed to... more
The coronary artery produces large amounts of prostacyclin (PGI2) and a small amount of thromboxane A2 (TXA2); this high PGI2/TXA2 ratio contributes to the antithrombotic properties of the coronary artery. This study was designed to determine whether this ratio changes after coronary artery thrombosis and thrombolysis and accounts for coronary artery reocclusion. Anesthetized dogs (N = 12) were subjected to electrically induced coronary artery thrombosis and tissue plasminogen activator-induced thrombolysis. Thrombolysis was achieved in 11 dogs, and the coronary artery reoccluded in five of these dogs after the initial reperfusion. Spontaneous and ionophore A23,187-stimulated PGI2 and TXA2 synthesis in normal circumflex and ischemic-reperfused left anterior descending coronary artery segments was measured by radioimmunoassay of thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively. Production of TXA2 was 413% to 656% greater in left anterior descending segments (from the region of thrombosis and sites proximal and distal to the thrombus) compared with normal circumflex segments (p &amp;amp;lt; 0.001). Production of PGI2 was also increased but only by 46% to 80% in the left anterior descending segments compared with normal circumflex segments (p &amp;amp;lt; 0.05). TXA2 production was greater in coronary artery segments that reocculded compared with segments that stayed open (p &amp;amp;lt; 0.02). Scanning electron microscopy revealed platelet deposition in thrombosed left anterior descending segments but not in segments proximal or distal to the thrombus site, indicating that the vascular wall per se may be a source of increased production of TXA2.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Interests: Cardiology, Scanning Electron Microscopy, Medicine, Dogs, Internal Medicine, and 15 moreFemale, Animals, Male, Artery, Recurrence, Public health systems and services research, American Heart Association, Tissue Plasminogen Activator, Thrombolytic Therapy, Indomethacin, epoprostenol, Prostacyclin, Cardiovascular medicine and haematology, Thrombus, and Coronary Vessels
The coronary artery often reoccludes soon after the flow has been restored with recombinant tissue-type plasminogen activator (TPA) in dogs with electrically-induced thrombosis. The coronary artery reocclusion relates to intense in situ... more
The coronary artery often reoccludes soon after the flow has been restored with recombinant tissue-type plasminogen activator (TPA) in dogs with electrically-induced thrombosis. The coronary artery reocclusion relates to intense in situ platelet activation and thrombin generation in the reperfused coronary artery. To determine the effect of a potent platelet inhibitor, the prostacyclin analog iloprost, in the prevention of coronary artery reocclusion, an occlusive thrombus was created in the left anterior descending coronary artery in 23 dogs. Coronary artery reflow occurred in 17 dogs after TPA (1 mg/kg over 20 minutes intravenously) administration. After the reflow was established, 10 dogs were given saline and 7 dogs were given iloprost (4 micrograms/kg over 40 minutes). In the saline-treated group, the coronary artery reoccluded in 8 of 10 dogs over 90 minutes (reocclusion rate 80%). In the iloprost-treated group, the coronary artery reoccluded in five of seven dogs (reocclusion rate 71%; p = NS vs TPA alone). The magnitude of peak coronary blood flow and duration of flow were similar in dogs given saline or iloprost after TPA-induced thrombolysis. Scanning electron microscopy showed residual thrombus and the appearance of coronary arterial narrowing distal to the thrombus in all dogs examined. Thus residual thrombus formation and coronary artery narrowing continue to occur after TPA-induced thrombolysis in dogs whether the animals are treated with saline or iloprost. Administration of iloprost after reflow does not modulate the frequency of coronary artery reocclusion.
Research Interests: Cardiology, Scanning Electron Microscopy, Medicine, Dogs, Internal Medicine, and 15 moreFemale, Animals, Male, Artery, Recurrence, Public health systems and services research, Time Factors, Coronary Circulation, American Heart Association, Tissue Plasminogen Activator, Thrombolytic Therapy, Thrombolysis, Cardiovascular medicine and haematology, Thrombus, and Coronary Vessels
Research Interests:
Research Interests: Medicine, Internal Medicine, Ischemia, Blood Pressure, Animals, and 14 moreMale, Heart, Fish Oil, Perfusion, Creatine Kinase, Clinical Nutrition(parenteral and Enteral Nutrition), Rats, Myocardium, Public health systems and services research, Coronary Circulation, American Heart Association, Indomethacin, Medical and Health Sciences, and Cardiovascular medicine and haematology
To determine the effects of peptide 6A (a fibrinogen‐degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50pmoles) caused a... more
To determine the effects of peptide 6A (a fibrinogen‐degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50pmoles) caused a short‐lasting dose‐dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 μmoles min‐1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 ± 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A‐induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6‐keto‐PGF1α in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A‐induced relaxation was abolished by de‐endothelialization, but not by treatment with indome...
Research Interests:
The pressure pulse contour in the ascending aorta of kangaroos is markedly different from that seen in other species, but the changes undergone by the pulse propagating along the aorta are quite similar. Alteration of wave contour and... more
The pressure pulse contour in the ascending aorta of kangaroos is markedly different from that seen in other species, but the changes undergone by the pulse propagating along the aorta are quite similar. Alteration of wave contour and progressive amplification of the pulse in the distal aorta and peripheral arteries of other mammals have been attributed to elastic nonuniformity of the aorta and to peripheral wave reflection. In kangaroos the aorta approximates a uniform tube with essentially constant viscoelastic properties, whereas wave reflection from the lower body appears to be unusually intense and to emanate from a single functionally discrete reflecting site; this appears to be the result of arterial terminations in the muscular lower body. Intense wave reflection from the lower body is the dominant mechanism responsible for changes in the pressure pulse of kangaroos between the ascending aorta and peripheral arteries. Contour of the pulse in the ascending aorta is attributab...
Research Interests:
Total left ventricular external power and aortic input impedance spectra were calculated from recordings of pulsatile pressure and flow in the ascending aorta of 22 human subjects undergoing cardiac catheterization. Eleven subjects had... more
Total left ventricular external power and aortic input impedance spectra were calculated from recordings of pulsatile pressure and flow in the ascending aorta of 22 human subjects undergoing cardiac catheterization. Eleven subjects had increased aortic pressure (systolic 153 +/- 3.8[SEM] mm Hg, p less than .001; diastolic 91 +/- 2.4 mm Hg, p less than .03; mean 118 +/- 2.4 mm Hg, p less than .001) and constituted the group with mild hypertension (average age 50 +/- 1.9 years). The other 11 (age-matched) subjects had normal arterial pressures and constituted the control group. Cardiac output in the hypertensive group was abnormally high (6.9 +/- 0.3 liters/min, p less than .04) compared with that in control subjects (6.1 +/- 0.2 liters/min), so that peripheral resistance was similar. Characteristic aortic impedance (index of aortic elastance) was increased in the hypertensive group (142 +/- 19 vs 72 +/- 4.5 dyne-sec-cm-5, p less than .002), as was the fluctuation of impedance moduli ...
Research Interests: Cardiology, Medicine, Humans, Internal Medicine, Hypertension, and 15 moreHemodynamics, Blood Pressure, Heart rate, Heart, Clinical Sciences, Middle Aged, Cardiac Output Monitoring, Circulation, Aorta, Blood Flow Velocity, Aortic pressure, Cardiac output, Diastole, Cardiovascular medicine and haematology, and ascending aorta
Research Interests:
It is paradoxical that this book on ventricular/vascular coupling will occupy space in medical libraries alongside clinical texts on hypertension, cardiac failure, and ischemic heart disease. Paradoxical, because the approaches described... more
It is paradoxical that this book on ventricular/vascular coupling will occupy space in medical libraries alongside clinical texts on hypertension, cardiac failure, and ischemic heart disease. Paradoxical, because the approaches described here are rarely if ever addressed in these clinical texts, even though they are of paramount relevance and importance. Neglect of these approaches is all the more surprising when one considers that hypertension, cardiac failure, and ischemic heart disease are among the most common serious diseases handled regularly by practicing physicians.
Research Interests:
Research Interests: Medicine, Dogs, Platelet aggregation, Hemodynamics, Female, and 15 moreAnimals, Male, Anesthesia, Recurrence, Coronary heart disease, Public health systems and services research, Combination drug therapy, Coronary Circulation, Tissue Plasminogen Activator, Platelet Count, Thrombolytic Therapy, The American, Nitroglycerin, Thrombolysis, and Cardiovascular medicine and haematology
Research Interests:
Research Interests:
Research Interests: Medicine, Dogs, Fibrin, Female, Animals, and 15 moreMale, Platelet activation mechanism, Recurrence, Plasminogen, Public health systems and services research, Saline, Recombinant Proteins, Fibrinolysis, Plasminogen Activator Inhibitor, Plasminogen Activator, The American, plasmin, Thrombolysis, Drug synergism, and Cardiovascular medicine and haematology
Research Interests:
Research Interests: Cardiology, Medicine, Humans, Internal Medicine, Hypertension, and 15 moreHemodynamics, Blood Pressure, Male, The, Clinical Sciences, Middle Aged, Aorta, Heart Ventricles, Brachial artery, Atenolol, Aortic pressure, carvedilol, Antihypertensive agents, Cardiovascular medicine and haematology, and Medical biochemistry and metabolomics
Previous studies indicate impairment of coronary arterial ring relaxation in response to acetylcholine (ACh) following coronary reperfusion, mediated via loss of endothelium-derived relaxing factor (EDRF). To examine if coronary... more
Previous studies indicate impairment of coronary arterial ring relaxation in response to acetylcholine (ACh) following coronary reperfusion, mediated via loss of endothelium-derived relaxing factor (EDRF). To examine if coronary vasodilator reserve is reduced following coronary occlusion-reperfusion in intact animals, 16 open-chest mongrel dogs were subjected to 1 hour of total left circumflex (Cx) coronary artery occlusion followed by reperfusion for 1 hour. Prior to Cx occlusion, coronary blood flow increased and vascular resistance decreased (both p less than or equal to 0.01) in response to ACh and bradykinin (BK). Following reperfusion, increase in Cx coronary flow in response to both vasodilators was significantly (p less than or equal to 0.01) impaired. Myocardial histology showed extensive neutrophil infiltration and capillary plugging by neutrophils in the Cx compared with the left anterior descending coronary artery-supplied myocardium. Myocardial myeloperoxidase activity ...
Research Interests: Cardiology, Medicine, Dogs, Peroxidase, Internal Medicine, and 15 moreHemodynamics, Female, Animals, Male, Acetylcholine, Clinical Sciences, Myocardium, Occlusion, Circulation, Coronary Circulation, Vasodilation, Indomethacin, Bradykinin, Cardiovascular medicine and haematology, and Coronary Vessels
Research Interests:
Research Interests:
Research Interests: Scanning Electron Microscopy, Medicine, Dogs, Heparin, Animals, and 13 moreAnesthesia, Recurrence, Public health systems and services research, Saline, Coronary Circulation, American Heart Association, Tissue Plasminogen Activator, Recombinant Proteins, Thrombolytic Therapy, Thrombolysis, Cardiovascular medicine and haematology, Thrombus, and Coronary Vessels
Research Interests: Pathology, Medicine, Platelet, Humans, Platelet aggregation, and 15 moreCholesterol, Animals, Clinical Sciences, Rats, Rat, In Vitro Studies, Aorta, Ferric Compounds, Lipoprotein a, Chlorides, Abdominal Aorta, delay time, Platelet Aggregation Inhibitors, Aorta Abdominal, and Cardiovascular medicine and haematology
The aim was to examine the effect of glyceryl trinitrate, a potent coronary vasodilator, on the thrombolytic effects of tissue type plasminogen inhibitor (t-PA) in dogs with coronary thrombosis. The thrombus was formed by delivery of... more
The aim was to examine the effect of glyceryl trinitrate, a potent coronary vasodilator, on the thrombolytic effects of tissue type plasminogen inhibitor (t-PA) in dogs with coronary thrombosis. The thrombus was formed by delivery of anodal direct current into the left anterior descending coronary artery. Fourteen dogs were randomly given t-PA alone (0.75 mg.kg-1 over 20 min) or t-PA with glyceryl trinitrate (125 micrograms.min-1 for 40 min). In four other dogs, glyceryl trinitrate was given after t-PA induced thrombolysis. Its effect on t-PA induced thrombolysis, in terms of reperfusion rate, time to thrombolysis, peak coronary blood flow, and reocclusion rate, was quantitated. Peripheral blood platelet counts and whole blood platelet aggregation were measured in all dogs. The thrombosed left anterior descending artery and normal circumflex coronary artery segments were examined by scanning electron microscopy at the end of the experiment. The reperfusion rate in the t-PA plus glyceryl trinitrate (t-PA + GTN) group was 57% (4/7 dogs) and with t-PA alone, 71% (5/7 dogs). The time to thrombolysis in the t-PA + GTN group was greater than with t-PA alone, at 30(SD 10) v 18(7) min, p less than 0.02, and the duration of reperfusion much shorter, at 11(17) v 48(15) min, p less than 0.02. Peak coronary blood flow in the t-PA + GTN group following reperfusion was less compared with t-PA alone, at 36(52) v 53(18) ml.min-1, p less than 0.02. Reocclusion rates in the two groups were similar. Peripheral blood platelet counts decreased during thrombus formation in all dogs; this decrease stabilised when t-PA was given alone but not when it was given with glyceryl trinitrate [mean platelet count at the end of t-PA infusion 7.23(1.68) and 4.78(3.00) X 10(8).ml-1 respectively, p less than 0.02], suggesting continued sequestration of platelets in the intracoronary thrombus in the latter group. Whole blood platelet aggregation decreased significantly with t-PA alone, but less so with t-PA + GTN [magnitude of platelet aggregation 0.23(0.57) and 5.67(6.23) ohms, respectively, p less than 0.02], suggesting lower plasma concentrations of t-PA when given with glyceryl trinitrate. Glyceryl trinitrate given after thrombolysis induced by t-PA failed to sustain reperfusion. Scanning electron microscopy of occluded left anterior descending artery showed extensive endothelial injury and a thrombus composed of platelet--red blood cells--fibrin mesh. The reperfused left anterior descending artery showed extensive endothelial injury and residual thrombus consisting mostly of fibrin and red blood cells with some platelets. Glyceryl trinitrate given concurrently with t-PA or after t-PA induced thrombolysis does not modify the thrombolytic potential of t-PA. The potentially &quot;detrimental&quot; effects of glyceryl trinitrate may be due to increase in hepatic blood flow and subsequent enhanced catabolism of t-PA. Lack of any significant effect of therapeutic dosage of glyceryl trinitrate on platelet--fibrin rich thrombus may explain the absence of a salutary action of this agent. Dynamic coronary vasoconstriction does not play an important role in coronary reocclusion after initial thrombolysis.
Research Interests: Cardiology, Cardiovascular, Scanning Electron Microscopy, Medicine, Dogs, and 15 moreBlood Pressure, Animals, Heart rate, Artery, Thrombosis, Combination drug therapy, Tissue Plasminogen Activator, Platelet Count, Thrombolytic Therapy, Plasminogen Activator, Nitroglycerin, Thrombolysis, Cardiovascular medicine and haematology, Thrombus, and Coronary Vessels
This study seeks to explain mechanisms responsible for the peculiar ascending aortic pressure waveform and impedance spectral pattern in kangaroos. Pulsatile pressure and blood flow velocity were measured and input impedance calculated in... more
This study seeks to explain mechanisms responsible for the peculiar ascending aortic pressure waveform and impedance spectral pattern in kangaroos. Pulsatile pressure and blood flow velocity were measured and input impedance calculated in the ascending aorta, descending thoracic aorta, and brachiocephalic artery of 15 rock kangaroos. Pressure and velocity waveforms and impedance spectral patterns were interpreted with the aid of an asymmetric uniform T-tube model of the systemic arterial tree. The ascending aortic pressure waveform displayed a very large secondary wave that began in late systole or early diastole and continued throughout most of diastole. The peak of this secondary wave (which almost always occurred in diastole) was often greater than peak systolic pressure and results from apparently intense wave reflections from peripheral vascular beds. This contention is supported by the configuration of the impedance spectral pattern that is explained on the basis of a single (...
Research Interests:
This study seeks to explain mechanisms responsible for the peculiar ascending aortic pressure waveform and impedance spectral pattern in kangaroos. Pulsatile pressure and blood flow velocity were measured and input impedance calculated in... more
This study seeks to explain mechanisms responsible for the peculiar ascending aortic pressure waveform and impedance spectral pattern in kangaroos. Pulsatile pressure and blood flow velocity were measured and input impedance calculated in the ascending aorta, descending thoracic aorta, and brachiocephalic artery of 15 rock kangaroos. Pressure and velocity waveforms and impedance spectral patterns were interpreted with the aid of an asymmetric uniform T-tube model of the systemic arterial tree. The ascending aortic pressure waveform displayed a very large secondary wave that began in late systole or early diastole and continued throughout most of diastole. The peak of this secondary wave (which almost always occurred in diastole) was often greater than peak systolic pressure and results from apparently intense wave reflections from peripheral vascular beds. This contention is supported by the configuration of the impedance spectral pattern that is explained on the basis of a single (...
Research Interests:
... USA. Sponsorship: Michael O'Rourke is a Director of Atcor Medical Pty. Limited, Sydney, Australia, manufacturer of systems for pulse wave analysis. ... Australia. Sponsorship: Michael O'Rourke is a Director of Atcor Medical... more
... USA. Sponsorship: Michael O'Rourke is a Director of Atcor Medical Pty. Limited, Sydney, Australia, manufacturer of systems for pulse wave analysis. ... Australia. Sponsorship: Michael O'Rourke is a Director of Atcor Medical Pty. ...
Research Interests:
To understand the influence of the aging process on left ventricular/arterial coupling (or interaction), it is important first to consider the effects of age on ventricular and arterial functions separately. The function of the left... more
To understand the influence of the aging process on left ventricular/arterial coupling (or interaction), it is important first to consider the effects of age on ventricular and arterial functions separately. The function of the left ventricle is to pump blood (the cardiac output) through the systemic arterial system to the organs and tissues in an amount sufficient to meet their metabolic requirements. The arterial system has two distinct and separate functions: (1) It serves as a vascular conduit system that delivers blood at high pressure to the various peripheral beds and (2) it serves as a buffering system (Windkessel) that smooths out pulsations resulting from intermittent ventricular ejection so that the capillaries receive a steady or continuous flow of blood.