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Biomedical subjects

W Grossman

Publications and source records attributed to W Grossman.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of coronary venous pressure on left ventricular diastolic distensibility.

Coronary arterial pressure and flow are known to influence left ventricular (LV) diastolic distensibility, but the influence of coronary venous pressure is unknown. To test the hypothesis that increased coronary venous pressure leads to an increase in LV wall volume and a decrease in LV diastolic distensibility, we studied excised, blood-perfused LV isovolumic dog hearts without the pericardium. In protocol I (n = 8), to raise coronary venous pressure the pressure of right atrium (RA) and right ventricle (RV) was increased by the height of a blood reservoir connected with a cannula that opened in both the RA and RV. In protocol II (n = 7), to isolate the effect of RV enlargement on LV diastolic distensibility (direct ventricular interaction), an isovolumic RV balloon was used with coronary venous pressure held constant at 0 mm Hg. Changes in LV diastolic distensibility were assessed by shifts of the LV end-diastolic pressure-volume relation. Changes in LV wall volume were detected by subepicardial segment length at end-diastole. The mean pressures of RA and RV (protocol I) and RV balloon only (protocol II) were increased from 0 to 15 and 30 mm Hg over a range of LV volume. In protocol I, when RA.RV pressure was increased from 0 to 30 mm Hg at three levels of LV volume (22 +/- 2, 31 +/- 3, and 40 +/- 3 ml), LV end-diastolic pressures increased significantly from 5.2 +/- 0.3 to 11.2 +/- 1.5, from 10.4 +/- 0.3 to 18.2 +/- 1.2, and from 20.2 +/- 1.0 to 28.8 +/- 1.2 mm Hg, respectively. In protocol II, when RV balloon pressure was increased from 0 to 30 mm Hg at the three LV volumes (21 +/- 3, 31 +/- 3, and 41 +/- 4 ml), LV end-diastolic pressures showed smaller increases from 5.2 +/- 0.2 to 6.6 +/- 0.2, from 9.8 +/- 0.3 to 11.6 +/- 0.6, and from 19.0 +/- 0.5 to 21.4 +/- 0.8 mm Hg, respectively. In both protocols, the LV end-diastolic pressure-volume relation shifted upward in a nearly parallel fashion, but the shift was much greater in protocol I than in protocol II. Despite constant LV volume, an increase in LV wall dimension in protocol I was significant and much greater than that in protocol II. From these results, we conclude that increased coronary venous pressure decreases LV diastolic distensibility with increasing LV wall volume, and this mechanism appears to act independently of diastolic ventricular interaction caused by RV enlargement.

Animals↗
PubMed1990

Diastolic dysfunction and congestive heart failure.

Diastolic heart failure is characterized by increased resistance to diastolic filling of one or both cardiac ventricles. Although some degree of diastolic failure exists in most patients presenting clinically with heart failure, a substantial subset of patients have relatively pure diastolic heart failure with normal systolic function. Diastolic heart failure can be due to structural abnormalities that increase resistance to ventricular inflow, and these structural abnormalities can be extramyocardial (e.g., constrictive pericarditis and mitral stenosis) or intramyocardial (e.g., fibrosis and amyloidosis). In addition to structural abnormalities, physiological derangement of myocardial inactivation and relaxation can contribute importantly to diastolic dysfunction in patients with heart failure. There is mounting evidence that advanced myocardial hypertrophy is associated with increased resistance to ventricular diastolic inflow due to both structural alteration (increased wall thickness and altered collagen matrix) and impaired diastolic relaxation of the hypertrophied myocardium. Physiological mechanisms for impaired relaxation in advanced hypertrophy remain controversial but can include disordered function of myocardial sarcoplasmic reticulum, subendocardial ischemia, and altered adenylate cyclase function. Diastolic dysfunction can play an important role in the genesis of flash pulmonary edema seen in patients with ischemic heart disease because myocardial ischemia is associated with a decline in relaxation rate, increased resistance to early diastolic filling, and in some cases, a striking upward shift in the left ventricular diastolic pressure-volume relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗
PubMed1990

Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure.

Intracellular Ca2+ release and reuptake are necessary for normal contraction and relaxation of the human heart. Intracellular Ca2+ transients were recorded with aequorin during isometric contraction of myocardium from patients with end-stage heart failure. In contrast to controls, contractions and Ca2+ transients of muscles from failing hearts were markedly prolonged, and the Ca2+ transients exhibited two distinct components. Muscles from the failing hearts showed a diminished capacity to restore a low resting Ca2+ level during diastole. These data obtained in actively contracting human myocardium suggest that intracellular Ca2+ handling is abnormal and might cause both systolic and diastolic dysfunction in heart failure. The inotropic effectiveness of drugs that act to increase intracellular levels of cyclic adenosine monophosphate (AMP), such as beta-adrenergic agonists and phosphodiesterase inhibitors, was markedly reduced in muscles from patients with heart failure. In contrast, the effectiveness of inotropic stimulation with drugs that act by cyclic AMP-independent mechanisms, such as the cardiotonic steroids and DPI 201-106, were preserved. Stimulation of intracellular cyclic AMP production by the adenylate cyclase activator forskolin restored the inotropic response to phosphodiesterase inhibitors. These studies indicate that an abnormality in cyclic AMP production may be a fundamental defect in patients with end-stage heart failure that may markedly diminish the effectiveness of agents that depend on generation of this nucleotide for a positive inotropic effect. Moreover, deficient production of cyclic AMP seems, at least in part, to account for the reversal of the force-frequency relation that characterizes failing myocardium. Of interest, direct measurement of total cellular cyclic AMP content and protein kinase activity did not reveal significant differences between the control and myopathic tissue, suggesting the presence in human ventricular muscle of physiologically distinct compartmentalized pools of cyclic AMP. Finally, changes in the sensitivity of the contractile apparatus to Ca2+ also seem to play an important role in the differential responsiveness to drugs of myopathic versus normal human myocardium.

Calcium↗
PubMed1990

Risk contracting.

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Accounting↗
PubMed1989

Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio.

One hundred one patients with coronary artery disease and pretreatment ratios of total cholesterol to high density lipoprotein (HDL) cholesterol greater than 4.0 were treated with niacin, commencing at low dosages (100 to 250 mg twice daily) and gradually increasing the dosage over 4 to 8 weeks to 1,000 mg twice daily. Dosage adjustments were made to minimize side effects. At a mean follow-up duration of 11 +/- 7 months, and a mean dosage of 1,415 +/- 698 mg/day, the group had a 13% reduction in total cholesterol, 31% increase in HDL and 32% decrease in the cholesterol to HDL ratio. A subgroup of 62 patients taking greater than 1,000 mg/day of niacin had an 18% reduction in total cholesterol, 32% increase in HDL and 36% improvement in the cholesterol to HDL ratio. A subgroup of 39 patients taking less than or equal to 1,000 mg/day of niacin had only a 5% reduction in total cholesterol, although a 29% increase in HDL and a 24% decrease in the cholesterol to HDL ratio were recorded. Side effects of niacin were reported in 38% of the patients, but led to discontinuation of therapy in only 4. Niacin can be administered in a fashion that is well tolerated, inexpensive and very effective in improving the cholesterol to HDL ratio.

Adult↗
PubMed1989

Randomised trial of fish oil for prevention of restenosis after coronary angioplasty.

To examine the potential role of fish oil supplementation in the prevention of restenosis after coronary angioplasty (PTCA), a randomised double-blind trial was conducted in 204 patients. The treatment group received 6 g/day of n-3 fatty acids, beginning 5.4 (SD 3.2) days before PTCA, and continuing for 6 months; the control group received olive oil placebo. Compliance was assessed by pill count and plasma levels of eicosapentaenoic acid (EPA). Restenosis was identified by symptoms and exercise testing and confirmed by angiography. PTCA was successful in 186 patients (93%). The incidence of angiographic restenosis was 34% in the fish oil group and 23% in the control group (relative risk 1.7, 95% CI 0.9-3.4). The lack of benefit of fish oil was not influenced by length of pretreatment, compliance with study medication, or the concentrations of plasma EPA achieved.

Angioplasty, Balloon↗
PubMed1989

The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease.

STUDY OBJECTIVE: To determine whether acute oral caffeine ingestion by patients with coronary artery disease results in decreased treadmill exercise performance or deterioration of echocardiographic measures of systolic or diastolic left ventricular function. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral-based cardiovascular exercise laboratory at an urban teaching hospital. PATIENTS: Thirteen volunteers with clinically stable coronary artery disease who had exercise tests after a 2-week caffeine-free washout period. Patients continued treatment with standard antianginal medications during the study period. INTERVENTIONS: Maximal exercise treadmill testing and exercise echocardiography were done at baseline, after acute ingestion of a placebo beverage (97% caffeine-free coffee), or after drinking an identical beverage containing 250 mg of caffeine sodium benzoate. MEASUREMENTS AND MAIN RESULTS: Acute ingestion of caffeine produced a serum level of 4.50 +/- 0.16 micrograms/mL, but had no effect on resting supine heart rate, blood pressure, left ventricular fractional shortening, posterior left ventricular wall thinning or peak rates of increase in left ventricular diastolic dimension. Despite a small increase in peak systolic blood pressure during exercise (baseline, 153 +/- 8; placebo, 154 +/- 8; caffeine, 161 +/- 7 mm Hg; P less than 0.05), exercise duration, time to onset of angina, and time to 0.1 mV ST depression did not differ after ingestion of placebo or caffeine. Rate-pressure product at onset of angina and onset of 0.1 mV of ST depression were also unchanged. In response to exercise, echocardiographic measures of left ventricular systolic and diastolic function were unchanged after caffeine compared with placebo ingestion. CONCLUSIONS: These data suggest that patients with exercise-induced ischemia who are receiving appropriate antianginal therapy tolerate the caffeine-equivalent of three cups of coffee without detrimental effect on intensity of ischemia, myocardial function, or exercise duration.

Adult↗
PubMed1989

Assessment of right atrial pressure-volume relations in patients with and without an atrial septal defect.

Assessment of the complex relations between pressure and volume in the right atrium has been hampered in the past by difficulties in the measurement of atrial volume. Accordingly, in the present study the dynamics of right atrial pressure-volume relations were examined (with the use of an impedance catheter to measure right atrial volume) in patients with and without an atrial septal defect. Right atrial pressure and impedance volume were measured in 16 patients at the time of cardiac catheterization with the use of a multi-electrode impedance catheter to provide continuous, on-line, pressure-volume data. Eleven patients without evidence of an interatrial shunt were examined during normal respiration and during the Valsalva maneuver and contrasted with five patients with an atrial septal defect documented by oxygen saturation step-up and echocardiographic studies. Right atrial pressure-volume diagrams in patients without an atrial septal defect exhibited the normal figure eight pattern, with an A loop (atrial contraction) and a V loop (passive filling), corresponding to the A wave and V wave of right atrial pressure, respectively. During inspiration, mean right atrial pressure decreased and mean right atrial volume increased, consistent with augmented venous return. With the Valsalva maneuver, right atrial pressure increased and both right atrial stroke volume and mean right atrial volume decreased compared with baseline. Patients with an atrial septal defect demonstrated baseline pressure-volume diagrams similar to those of patients without an interatrial shunt. However, no change in mean right atrial volume occurred with either respiration or the Valsalva maneuver despite changes in right atrial pressure similar to those seen inpatients without an atrial septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Human lung carcinoma monoclonal antibody specific for the Thomsen-Friedenreich antigen.

A monoclonal antibody, RS1-114, was raised against the human adenocarcinoma of the lung cell line A549. By studying the reactivity of RS1-114 with A549 cells following chemical and enzymatic treatments, it was shown that the epitope is a galactose-containing carbohydrate, which is devoid of sialic acid. Hemagglutination of desialylated RBCs, enzyme-linked immunosorbent assay studies with glycoprotein antigens before and after desialylation, and competition studies using peanut agglutinin indicate that monoclonal antibody RS1-114 recognizes the Thomsen-Friedenreich antigen, a cryptic determinant on human erythrocytes which can be exposed by neuraminidase treatment. It is expressed in an unhidden form on a large percentage of carcinomas and is therefore an important human tumor marker. RS1-114 is reactive with cryptic determinants of the Thomsen-Friedenreich antigen on white blood cells as well as red blood cells, and it reacts with unhidden determinants on human tumor cell lines. The number of binding sites on carcinoma cells is further increased by neuraminidase treatment. By immunohistochemical staining, it was shown that 75% of the human tumors tested are reactive with RS1-114. These include tumors of the breast, colon, lung, kidney, ovary, and rectum.

Adenocarcinoma↗
PubMed1989

Mechanisms of positive inotropic effects and delayed relaxation produced by DPI 201-106 in mammalian working myocardium: effects on intracellular calcium handling.

1. We used the bioluminescent protein aequorin, which emits light when it combines with Ca2+, to test the hypothesis that the inotropic and lusitropic actions of DPI 201-106 are due to changes in intracellular Ca2+ handling in papillary muscles from ferrets and guinea-pigs. 2. DPI 201-106 increased peak isometric tension (T) in a dose-dependent manner, with an 83% increase in T as the concentration of DPI 201-106 was increased to 1 x 10(-5) M; however, peak [Ca2+]i did not increase significantly until the concentration of DPI 201-106 reached 3 x 10(-6) M, suggesting a sensitization of the contractile apparatus to Ca2+. 3. Tetrodotoxin (1 x 10(-6) M), which did not reduce the tension response significantly before DPI 201-106, decreased both [Ca2+]i and T in the presence of 1 x 10(-5) M DPI 201-106, suggesting involvement of a sodium channel activation mechanism; however, tetrodotoxin did not completely reverse the calcium sensitization. 4. The shift of the [Ca2+]i versus T relationship was not observed in the presence of another sodium channel agonist, veratridine (3 x 10(-7)-1 x 10(-6) M). 5. In the guinea-pig, DPI 201-106 markedly prolonged relaxation of tension (increase of 60% in the time from peak to 50% tension regression), which was accompanied by the appearance of a second component in the aequorin light signal; effects on relaxation were less prominent in the ferret. 6. Tension prolongation and the second component of the [Ca2+]i transient in the guinea-pig were exacerbated by increased [Ca2+]o and decreased by tetrodotoxin. Ryanodine (3 x 10(-7) M) markedly diminished the calcium transient in controls and the initial component of the calcium transient in the presence of DPI 201-106, but had only a modest effect on the second component. 7. We conclude that although sodium agonism plays a role, sensitization of the contractile apparatus to Ca2+ is an important mechanism in the positive inotropic action of DPI 201-106. 8. The negative lusitropic action of DPI 201-106 varies between ferret and guinea-pig, possibly reflecting differences between these two species in subcellular Ca2+ handling.

Aequorin↗
PubMed1989

Progressive improvement in pulmonary vascular resistance after percutaneous mitral valvuloplasty.

Percutaneous mitral valvuloplasty has been proposed as a nonsurgical technique for treating high-risk patients with mitral stenosis who are deferred from mitral valve replacement. The effect of this technique on patients with pulmonary hypertension, however, has not been fully evaluated. Accordingly, serial assessment of pulmonary vascular resistance was made in 14 patients with critical mitral stenosis and pulmonary hypertension (pulmonary vascular resistance greater than 250 dynes.sec/cm5 or mean pulmonary artery pressure greater than 40 mm Hg or both) who underwent percutaneous balloon dilatation of the mitral valve. Balloon valvuloplasty was performed with either one (n = 10) or two (n = 4) balloons through the transseptal approach, and it resulted in significant improvement in mean mitral gradient (from 18 +/- 4 to 9 +/- 4 mm Hg, p less than 0.001), systemic blood flow (from 3.7 +/- 1.2 to 5.0 +/- 2.2 l/min, p less than 0.001), and calculated mitral valve area (from 0.7 +/- 0.2 to 1.6 +/- 0.7 cm2, p less than 0.001). Immediately after balloon mitral valvuloplasty, pulmonary vascular resistance fell from 630 +/- 570 to 447 +/- 324 dynes.sec/cm5. Repeat catheterization 7 +/- 4 months after valvuloplasty showed further improvement of pulmonary hypertension in 12 of the 14 patients, with a mean pulmonary vascular resistance for the group as a whole of 280 +/- 183 dynes.sec/cm5, p less than 0.005. In two patients, mitral valve restenosis to a mitral valve area less than 1.0 cm2 was associated with a return of pulmonary hypertension to predilatation values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Differences in alpha-adrenergic responsiveness between human internal mammary arteries and saphenous veins.

Little is known regarding specific biologic and pharmacologic differences between human internal mammary arteries and saphenous veins. To better define the role of alpha-adrenoceptor-mediated vasoconstriction in human internal mammary arteries and saphenous veins, we obtained fresh specimens of both vessels from 32 patients undergoing coronary artery bypass surgery. Dose-response curves were generated for the relatively selective alpha 1-receptor agonist phenylephrine, the alpha 2-receptor agonist BHT-920, and the alpha 1- and alpha 2-receptor agonist norepinephrine. Phenylephrine elicited similar contractile responses in internal mammary arteries and saphenous veins, with a mean EC50 (the effective concentration necessary to produce 50% of the maximal contraction) of 1.4 X 10(-6) M for internal mammary arteries and 1.8 X 10(-6) M for saphenous veins (p = NS). Selective stimulation of alpha 2-receptors with BHT-920 elicited a marked contractile response only in saphenous veins. Dose-response curves for phenylephrine and BHT-920 were shifted to the right for both vessels in the presence of the alpha 1-receptor antagonist prazosin and the alpha 2-receptor antagonist yohimbine, respectively. Norepinephrine elicited contraction at a lower concentration in saphenous veins than in internal mammary arteries with a mean EC50 of 7.8 X 10(-8) M for saphenous veins and a mean EC50 of 3.4 X 10(-7) M for internal mammary arteries (p less than 0.05). The results suggest that alpha-adrenoceptor-mediated vasoconstriction is caused primarily by alpha 1-receptors in human internal mammary arteries and by alpha 1- and alpha 2-receptors in human saphenous veins.

Adrenergic alpha-Agonists↗
PubMed1989

Comparative effects of hypoxia and ischemia in the isolated, blood-perfused dog heart: evaluation of left ventricular diastolic chamber distensibility and wall thickness.

To compare the effects of hypoxia and ischemia on left ventricular (LV) diastolic function, we studied 17 isolated, isovolumic dog hearts by measuring LV diastolic chamber distensibility (LV end diastolic pressure at constant volume), wall thickness, and myocardial pH in response to hypoxia at constant coronary flow or pressure versus global ischemia (zero coronary blood flow). Hypoxic perfusates consisted of methemoglobin-containing red blood cells suspended in lactated Ringer's solution. Brief cross-clamping of the coronary perfusion line was used to assess the contribution of coronary turgor to chamber distensibility and wall thickness. With hypoxia, left ventricles showed a significant early (5 minutes) decrease in diastolic distensibility and an increase in wall thickness, at either constant coronary perfusion pressure or flow. The increase in wall thickness was independent of hypoxia-induced changes in coronary turgor. In contrast, global ischemia produced an early increase in LV diastolic chamber distensibility and a decrease in wall thickness. When global ischemia was continued beyond 60 minutes, a decrease in LV chamber distensibility developed. This diastolic contracture was not associated with an increase in LV wall thickness. Myocardial pH decreased slightly during 15 minutes of hypoxia and markedly with 15 minutes of global ischemia. Thus, LV diastolic chamber distensibility decreased during 15 minutes of hypoxia, while an increase in distensibility was seen during global ischemia of similar duration. During hypoxia, these changes were associated with increased LV wall thickness, at either constant coronary perfusion pressure or constant coronary flow. Prolonged ischemia led to diastolic contracture without an increase in wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Direct measurement of changes in intracellular calcium transients during hypoxia, ischemia, and reperfusion of the intact mammalian heart.

In studies of ischemia and reperfusion, a major experimental problem has been the inability to measure intracellular ionized calcium ([Ca2+]i) in the intact heart. We have developed a new approach in which the bioluminescent calcium indicator aequorin is used to measure [Ca2+]i in the isolated, coronary-perfused ferret heart. Aequorin is loaded into subepicardial myocytes of the left ventricle, and the signals are recorded simultaneously along with isovolumic left ventricular (LV) pressure at a constant pacing rate. This system shows 1) no attenuation or change of time course of LV pressure development or coronary perfusion pressure after aequorin loading; 2) consistent responses to physiological interventions and drugs; 3) individual aequorin and pressure signals that do not require signal averaging for analysis; and 4) [Ca2+]i levels comparable with those reported in tissue or isolated myocyte cell preparations. During 5 minutes of hypoxia, diastolic [Ca2+]i and LV diastolic pressure increased while the systolic values of both [Ca2+]i and pressure decreased. The peak-to-peak systolic [Ca2+]i versus LV isovolumic pressure relation remained close to the control curve. In contrast, during 3 minutes of global ischemia, LV systolic and diastolic pressures fell rapidly, while [Ca2+]i increased substantially. The [Ca2+]i versus pressure relations for both systole and diastole shifted to the right, indicating desensitization of the contractile apparatus to [Ca2+]i. These results provide evidence that different primary mechanisms determine the systolic and diastolic responses to acute hypoxia versus ischemia. During hypoxia, changes in [Ca2+]i handling probably play a major role, while during ischemia, changes in the Ca2+ sensitivity of the myofilaments appear to be of primary importance in the modulation of contractile dysfunction.

Aequorin↗
PubMed1989

Chronic exercise training protects aged cardiac muscle against hypoxia.

To test the hypothesis that chronic exercise may improve tolerance to hypoxia in aged hearts, we compared cardiac function of exercised rats to that of their age-matched, nonexercised controls. Right ventricular papillary muscles were removed from young adult (9 mo) and old (24-26 mo) male Fischer 344 rats that were chronically exercised on a rodent treadmill and from their age-matched, nonexercised controls. During isometric contraction, hypoxia depressed contraction and relaxation in all muscles, but to a lesser extent in the exercised groups. A significant exercise effect was observed in the following variables: the maximum developed tension, the maximum rate of tension development, the maximum rate of tension decline, and the time required for the hypoxia to reduce maximum tension by 20%. The maximum rate of tension decline was more sensitive to hypoxia than was the maximum rate of tension development in all groups. Exercise also had an effect on the temperature dependence of cardiac performance during hypoxia. Thus, chronic exercise results in the preservation of both contraction and relaxation during hypoxia for aged as well as young adult hearts.

Aging↗
PubMed1988

Percutaneous balloon mitral valvuloplasty in a pregnant woman with mitral stenosis.

A 39-year-old woman with symptomatic mitral stenosis underwent percutaneous mitral valvuloplasty at the end of her first trimester of pregnancy. Balloon dilatation utilizing a double 18-20 mm balloon technique resulted in improvement in mean mitral gradient (16 to 7 mmHg) and in calculated mitral valve area (1.4 to 2.4 cm2), without significant complications and with an estimated radiation exposure to the fetus of less than 0.2 rads. The procedure resulted in disappearance of symptoms of congestive heart failure and allowed for discontinuation of diuretics. The subsequent course of gestation was uncomplicated and a normal baby boy was delivered in the 36th wk. We conclude that percutaneous mitral valvuloplasty may produce successful palliation of symptoms in patients with mitral stenosis during pregnancy.

Adult↗