Bacterial endocarditis continues to cause high morbidity and mortality and often occurs in the se... more Bacterial endocarditis continues to cause high morbidity and mortality and often occurs in the setting of structural abnormalities of the cardiovascular system. Alterations of the normal heart valvular function increase the risk for that valve to become the site of a bacterial nidus. Patients with valve replacement, rheumatic valvular disease, or congenital heart malformations are among those at highest risk. Many medical, surgical, and dental procedures result in significant short-term bacteremia that places such patients at risk for infecting their heart valves. It is not a new concept that an antimicrobial agent present in the blood during the time a procedure-induced bacteremia occurs might prevent infective endocarditis. The American Heart Association (AHA), Dallas, Tex, issued its guidelines for prevention in 1965 with revisions in 1972, 1977, and 1984. 13 The most recent revision of these recommendations appeared December 12, 1990, in the Journal of the American Medical Association . 4 The
American Journal of Physiology-Heart and Circulatory Physiology, 1992
Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To ... more Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To determine whether the left ventricle from dogs with chronic norepinephrine infusion can sustain additional functional loads, we altered ventricular preload or afterload and determined both global and left ventricular (LV) wall function. Dogs were instrumented to measure LV wall function, LV internal base diameter, and LV pressures and were allowed to fully recover. Preload was altered by volume loading and afterload by injection of phenylephrine. Osmotic infusion pumps were implanted to continuously release norepinephrine at 0.5 micrograms.kg-1.min-1 for 28 days, and the volume loading and phenylephrine were repeated on days 14 and 28. Heart rate decreased, whereas there were no differences in mean arterial pressure, maximum first derivative of LV pressure (dP/dt), LV dP/dt/developed pressure of 40 mmHg, LV dP/dt/end-diastolic circumference, slope of the pressure-diameter relation, peak ...
Uptake and metabolism of biogenic amines in developing lung were studied in a total of 62 New Zea... more Uptake and metabolism of biogenic amines in developing lung were studied in a total of 62 New Zealand White rabbits aged 28 days of gestation to 28 days postnatal. Lungs were perfused in vitro with 5-[14C]hydroxytryptamine (5-HT) or [14C]phenylethylamine (PEA) and coperfused with high-molecular-weight [3H]dextran to assess the vascular space perfused. Patterns of uptake and metabolism of PEA and 5-HT as functions of age were markedly different. PEA uptake and metabolism gradually increased with advancing age. No differences were observed in 5-HT uptake or metabolism within the postnatal age range studied, but the magnitude of each process for 5-HT was significantly lower in premature animals. Functional maturity for both uptake and metabolism of PEA was observed by 14-21 days of age. Inhibition of intrapulmonary monoamine oxidase by semicarbazide and pargyline showed that PEA metabolism was unaffected by the former and moderately reduced by the latter agent only in animals older tha...
Present theories of cellular respiratory control suggest that the rate of ATP production by mitoc... more Present theories of cellular respiratory control suggest that the rate of ATP production by mitochondria is regulated by the local concentration of ATP, ADP, and inorganic phosphate. Furthermore, the term (ATP)/(ADP)(Pi), known as the phosphorylation ratio, characterizes the cellular energy balance between ATP use and production. Thus, changes in the rate of ATP use are reflected in changes in the phosphorylation ratio. In cellular systems, which contain creatine kinase such as skeletal muscle, brain, and heart, the rate of ATP use is also reflected in changes in the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), since the creatine kinase reaction is normally at or very near equilibrium.
Monocrotaline-induced pulmonary hypertension (PH) in rats is preceded by an inflammatory response... more Monocrotaline-induced pulmonary hypertension (PH) in rats is preceded by an inflammatory response in the lungs, and interleukin-6 (IL-6) is expressed in response to inflammation. To evaluate the role of IL-6 in monocrotaline-induced PH, rats received a single subcutaneous injection of monocrotaline (60 mg/kg) or an equivalent amount of normal saline. Pulmonary artery pressure (Ppa), right ventricular hypertrophy (RVH), expression of IL-6 mRNA, and bioactivity of IL-6 in the lungs of these rats were examined 48 hours and 1 and 2 weeks after administration of monocrotaline. The effects of dexamethasone treatment on monocrotaline-induced PH also were evaluated. Two weeks after administration of monocrotaline, significant PH and RVH developed in these rats. Reverse transcription-polymerase chain reaction (RT-PCR) revealed expression of IL-6 mRNA in the lungs 48 hours and 1 and 2 weeks after administration of monocrotaline. This was confirmed using ribonuclease protection assay. The bioa...
Extraction of circulating vasoactive hormones by the lung may influence systemic vasomotor tone. ... more Extraction of circulating vasoactive hormones by the lung may influence systemic vasomotor tone. Since this process occurs in the pulmonary microcirculation, we evaluated the effects of pulmonary artery hypertension (PAH) secondary to congenital heart disease (CHD) on this metabolic function of lung. Eleven patients with varying congenital cardiac lesions were studied preoperatively and postoperatively. Five had normal pulmonary artery pressure (PAP) (group I), and six had PAH with peak systolic PAP greater than 40 mm Hg (group II). PA and postpulmonary arterial blood samples were collected before and after surgery at the time of pressure measurements. Norepinephrine (NE) and epinephrine (EPI) levels were determined by radioenzymatic assay. Preoperatively, circulating NE levels were higher (P less than 0.05) and NE extraction measured was lower (P less than 0.01) in group II patients as compared with group I. Extraction increased in group II postoperatively after PA pressures were r...
Pulmonary extraction of radiolabeled norepinephrine (NE) was evaluated in newborn rabbits aged 1 ... more Pulmonary extraction of radiolabeled norepinephrine (NE) was evaluated in newborn rabbits aged 1 to 3 days. Twenty pups were raised from birth in an hypoxic environment (FiO2 = 0.16-0.17) and 10 were raised in room air for study as controls. NE extraction was measured using an isolated, perfused lung technique. In hypoxic animals, average percent removal of NE was significantly reduced (p less than 0.05) as compared to controls while pulmonary pressures were increased (p less than 0.05) compared to controls. The data suggest that hypoxia reduces the ability of the lung to clear norepinephrine. This may be a factor in systemic and pulmonary vasomotor responses to hypoxia.
Guidelines From the American Heart Association: A Guideline From the American Heart Association R... more Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on ...
The aim was to measure changes in atrial wall function over a wide range of atrial filling pressu... more The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters. During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1. Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.
Bacterial endocarditis continues to cause high morbidity and mortality and often occurs in the se... more Bacterial endocarditis continues to cause high morbidity and mortality and often occurs in the setting of structural abnormalities of the cardiovascular system. Alterations of the normal heart valvular function increase the risk for that valve to become the site of a bacterial nidus. Patients with valve replacement, rheumatic valvular disease, or congenital heart malformations are among those at highest risk. Many medical, surgical, and dental procedures result in significant short-term bacteremia that places such patients at risk for infecting their heart valves. It is not a new concept that an antimicrobial agent present in the blood during the time a procedure-induced bacteremia occurs might prevent infective endocarditis. The American Heart Association (AHA), Dallas, Tex, issued its guidelines for prevention in 1965 with revisions in 1972, 1977, and 1984. 13 The most recent revision of these recommendations appeared December 12, 1990, in the Journal of the American Medical Association . 4 The
American Journal of Physiology-Heart and Circulatory Physiology, 1992
Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To ... more Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To determine whether the left ventricle from dogs with chronic norepinephrine infusion can sustain additional functional loads, we altered ventricular preload or afterload and determined both global and left ventricular (LV) wall function. Dogs were instrumented to measure LV wall function, LV internal base diameter, and LV pressures and were allowed to fully recover. Preload was altered by volume loading and afterload by injection of phenylephrine. Osmotic infusion pumps were implanted to continuously release norepinephrine at 0.5 micrograms.kg-1.min-1 for 28 days, and the volume loading and phenylephrine were repeated on days 14 and 28. Heart rate decreased, whereas there were no differences in mean arterial pressure, maximum first derivative of LV pressure (dP/dt), LV dP/dt/developed pressure of 40 mmHg, LV dP/dt/end-diastolic circumference, slope of the pressure-diameter relation, peak ...
Uptake and metabolism of biogenic amines in developing lung were studied in a total of 62 New Zea... more Uptake and metabolism of biogenic amines in developing lung were studied in a total of 62 New Zealand White rabbits aged 28 days of gestation to 28 days postnatal. Lungs were perfused in vitro with 5-[14C]hydroxytryptamine (5-HT) or [14C]phenylethylamine (PEA) and coperfused with high-molecular-weight [3H]dextran to assess the vascular space perfused. Patterns of uptake and metabolism of PEA and 5-HT as functions of age were markedly different. PEA uptake and metabolism gradually increased with advancing age. No differences were observed in 5-HT uptake or metabolism within the postnatal age range studied, but the magnitude of each process for 5-HT was significantly lower in premature animals. Functional maturity for both uptake and metabolism of PEA was observed by 14-21 days of age. Inhibition of intrapulmonary monoamine oxidase by semicarbazide and pargyline showed that PEA metabolism was unaffected by the former and moderately reduced by the latter agent only in animals older tha...
Present theories of cellular respiratory control suggest that the rate of ATP production by mitoc... more Present theories of cellular respiratory control suggest that the rate of ATP production by mitochondria is regulated by the local concentration of ATP, ADP, and inorganic phosphate. Furthermore, the term (ATP)/(ADP)(Pi), known as the phosphorylation ratio, characterizes the cellular energy balance between ATP use and production. Thus, changes in the rate of ATP use are reflected in changes in the phosphorylation ratio. In cellular systems, which contain creatine kinase such as skeletal muscle, brain, and heart, the rate of ATP use is also reflected in changes in the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), since the creatine kinase reaction is normally at or very near equilibrium.
Monocrotaline-induced pulmonary hypertension (PH) in rats is preceded by an inflammatory response... more Monocrotaline-induced pulmonary hypertension (PH) in rats is preceded by an inflammatory response in the lungs, and interleukin-6 (IL-6) is expressed in response to inflammation. To evaluate the role of IL-6 in monocrotaline-induced PH, rats received a single subcutaneous injection of monocrotaline (60 mg/kg) or an equivalent amount of normal saline. Pulmonary artery pressure (Ppa), right ventricular hypertrophy (RVH), expression of IL-6 mRNA, and bioactivity of IL-6 in the lungs of these rats were examined 48 hours and 1 and 2 weeks after administration of monocrotaline. The effects of dexamethasone treatment on monocrotaline-induced PH also were evaluated. Two weeks after administration of monocrotaline, significant PH and RVH developed in these rats. Reverse transcription-polymerase chain reaction (RT-PCR) revealed expression of IL-6 mRNA in the lungs 48 hours and 1 and 2 weeks after administration of monocrotaline. This was confirmed using ribonuclease protection assay. The bioa...
Extraction of circulating vasoactive hormones by the lung may influence systemic vasomotor tone. ... more Extraction of circulating vasoactive hormones by the lung may influence systemic vasomotor tone. Since this process occurs in the pulmonary microcirculation, we evaluated the effects of pulmonary artery hypertension (PAH) secondary to congenital heart disease (CHD) on this metabolic function of lung. Eleven patients with varying congenital cardiac lesions were studied preoperatively and postoperatively. Five had normal pulmonary artery pressure (PAP) (group I), and six had PAH with peak systolic PAP greater than 40 mm Hg (group II). PA and postpulmonary arterial blood samples were collected before and after surgery at the time of pressure measurements. Norepinephrine (NE) and epinephrine (EPI) levels were determined by radioenzymatic assay. Preoperatively, circulating NE levels were higher (P less than 0.05) and NE extraction measured was lower (P less than 0.01) in group II patients as compared with group I. Extraction increased in group II postoperatively after PA pressures were r...
Pulmonary extraction of radiolabeled norepinephrine (NE) was evaluated in newborn rabbits aged 1 ... more Pulmonary extraction of radiolabeled norepinephrine (NE) was evaluated in newborn rabbits aged 1 to 3 days. Twenty pups were raised from birth in an hypoxic environment (FiO2 = 0.16-0.17) and 10 were raised in room air for study as controls. NE extraction was measured using an isolated, perfused lung technique. In hypoxic animals, average percent removal of NE was significantly reduced (p less than 0.05) as compared to controls while pulmonary pressures were increased (p less than 0.05) compared to controls. The data suggest that hypoxia reduces the ability of the lung to clear norepinephrine. This may be a factor in systemic and pulmonary vasomotor responses to hypoxia.
Guidelines From the American Heart Association: A Guideline From the American Heart Association R... more Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on ...
The aim was to measure changes in atrial wall function over a wide range of atrial filling pressu... more The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters. During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1. Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.
Uploads
Papers by M. Gewitz