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Biomedical subjects

W Grossman

Publications and source records attributed to W Grossman.

At least 55 records · Page 3Linked to original sources
PubMed1992

Decreased myofilament responsiveness in myocardial stunning follows transient calcium overload during ischemia and reperfusion.

The purpose of this study was to test the hypothesis that abnormal intracellular calcium handling characterizes myocardial stunning. Isolated, isovolumic, buffer-perfused ferret hearts were loaded with the bioluminescent calcium indicator aequorin for simultaneous measurement of individual calcium transients and left ventricular pressure. After 15 minutes of global ischemia and 20 minutes of reperfusion, left ventricular developed pressure was significantly reduced (75 +/- 7 versus 93 +/- 6 mm Hg, p < 0.05). During ischemia, [Ca2+]i levels were significantly elevated compared with preischemic levels, both during systole (1.38 +/- 0.31 versus 0.88 +/- 0.2 microM, p < 0.05) and end diastole (0.85 +/- 0.16 versus 0.38 +/- 0.13 microM, p < 0.05). Early during reperfusion, [Ca2+]i was also significantly elevated during systole (1.63 +/- 0.44 versus 0.88 +/- 0.20 microM, p < 0.05) and end diastole (0.75 +/- 0.15 versus 0.38 +/- 0.13 microM, p < 0.05). After 20 minutes of reperfusion, myocardial stunning occurred, but [Ca2+]i was not significantly different from preischemic levels. Thus, myocardial stunning does not result from decreased levels of activator calcium. The force-pCa relation generated by the stunned hearts was shifted downward compared with that generated by the control hearts, consistent with a decrease in maximum calcium-activated force (Fmax). At steady state during tetanus, the decrease in Fmax was confirmed, but there was no significant difference in the slope of the force-pCa relation of the stunned hearts versus controls. Thus, we conclude that stunned myocardium is characterized by decreased Fmax without desensitization of the myofilaments to [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1992

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

Cardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression of c-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of beta- to alpha-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca(2+)-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal alpha-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac alpha-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress.

Actins↗
PubMed1992

Intracellular calcium and ventricular function. Effects of nisoldipine on global ischemia in the isovolumic, coronary-perfused heart.

Ischemia-induced ventricular dysfunction has been shown to be associated with increased diastolic and systolic intracellular concentrations of free, ionized calcium ([Ca2+]i). The present study was designed to determine the effects of the Ca2+ antagonist nisoldipine on the relationship between [Ca2+]i and left ventricular contraction and relaxation during ischemia and reperfusion on a beat-to-beat basis. Nine isovolumic coronary-perfused ferret hearts were made globally ischemic for 3 min and reperfused for 10 min. Ischemia and reperfusion were repeated during perfusion with a buffer containing 10(-8) M nisoldipine. From left ventricular developed pressure, time to peak pressure and time to 50% pressure decline were obtained. [Ca2+]i was determined with the bioluminescent protein aequorin. Global ischemia caused a rapid decline in contractile function and a significant increase in diastolic [Ca2+]i, from 0.35 to 0.81 microM, and in systolic [Ca2+]i, from 0.61 to 0.96 microM. During reperfusion, [Ca2+]i returned to baseline while ventricular function was still impaired. Relaxation was more affected than systolic contractile function. Nisoldipine significantly reduced the ischemia-induced rise in diastolic [Ca2+]i to 0.62 microM, and in systolic [Ca2+]i to 0.77 microM, and lessened the decrease in contractile function. Nisoldipine significantly accelerated the decline in [Ca2+]i during reperfusion and improved recovery of contractility and relaxation. These effects were associated with a significant diminution in ischemic lactate production. Taken together, our results provide direct quantitative evidence on a beat-to-beat basis that the calcium antagonist nisoldipine can ameliorate ischemia-induced abnormalities in [Ca2+]i handling, an effect that was associated with improved myocardial function during early reperfusion.

Animals↗
PubMed1992

Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure.

Cytoplasmic free calcium ions (Ca2+) play a central role in excitation-contraction coupling of cardiac muscle. Abnormal Ca2+ handling has been implicated in systolic and diastolic dysfunction in patients with end-stage heart failure. The current study tests the hypothesis that expression of genes encoding proteins regulating myocardial Ca2+ homeostasis is altered in human heart failure. We analyzed RNA isolated from the left ventricular (LV) myocardium of 30 cardiac transplant recipients with end-stage heart failure (HF) and five organ donors (normal control), using cDNA probes specific for the cardiac dihydropyridine (DHP) receptor (the alpha 1 subunit of the DHP-sensitive Ca2+ channel) and cardiac calsequestrin of sarcoplasmic reticulum (SR). In addition, abundance of DHP binding sites was assessed by ligand binding techniques (n = 6 each for the patients and normal controls). There was no difference in the level of cardiac calsequestrin mRNA between the HF patients and normal controls. In contrast, the level of mRNA encoding the DHP receptor was decreased by 47% (P less than 0.001) in the LV myocardium from the patients with HF compared to the normal controls. The number of DHP binding sites was decreased by 35-48%. As reported previously, expression of the SR Ca(2+)-ATPase mRNA was also diminished by 50% (P less than 0.001) in the HF group. These data suggest that expression of the genes encoding the cardiac DHP receptor and SR Ca(2+)-ATPase is reduced in the LV myocardium from patients with HF. Altered expression of these genes may be related to abnormal Ca2+ handling in the failing myocardium, contributing to LV systolic and diastolic dysfunction in patients with end-stage heart failure.

Adolescent↗
PubMed1992

Capital PPS transition period affects timing differences.

The Health Care Financing Administration's new capital payment system means hospitals face timing differences in their financial statements. A hospital's 10-year transition into the new system could involve a switch from the hold-harmless payment method to the fully prospective method. To maximize the recoverability of deferred assets and liabilities, hospitals should understand the details of both methods and how changes in third-party payment programs can affect timing differences.

Accounting↗
PubMed1991

Excitation-contraction uncoupling during ischemia in the blood perfused dog heart.

The bioluminescent of Ca(2+)-indicator, aequorin, was loaded into the left ventricular apex of blood-perfused hearts from 13 dogs for simultaneous recording of left ventricular pressure and intracellular calcium levels. During a 2 minute period of ischemia, systolic and diastolic pressures significantly decreased. In contrast, these pressure changes were associated with an increase in both systolic and diastolic calcium reaching a maximum diastolic value of 0.59 microM and a systolic value of 1.11 microM. This apparent dissociation between pressure and [Ca2+]i supports the hypothesis that changes in myofilament Ca2+ responsiveness are of major importance in modulating contractility during ischemia in large mammalian hearts.

Aequorin↗
PubMed1991

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia.

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hemodynamic evaluation of a chronically implanted, electrically powered left ventricular assist system: responses to acute circulatory stress.

Hemodynamic stress testing was performed in four calves with a chronically implanted left ventricular assist device consisting of a double-valved pump interposed between the left ventricular apex and the descending thoracic aorta. The device was powered either pneumatically (n = 1) or with a transcutaneous energy transmission system (n = 3). Hemodynamic evaluation (cardiac output and right and left ventricular and pulmonary and carotid artery pressures) was carried out at baseline and during all hemodynamically stressed states. Atrial pacing and ventricular pacing to a heart rate of 140 beats/min resulted in no significant change in right or left heart filling pressures or cardiac output. Preload reduction with nitroprusside or transient inferior vena cava balloon occlusion resulted in a marked decrease in left ventricular pressure with preservation of mean arterial pressure. Phenylephrine administration resulted in a marked rise in mean arterial pressure with no change in cardiac output or filling pressure. Induction of ventricular fibrillation resulted in a decrease of mean left ventricular pressure to 11 +/- 8 mm Hg, but mean arterial pressure was maintained at greater than or equal to 50 mm Hg. It is concluded that a multicomponent, implantable, electrically powered assist system is capable of maintaining a normal cardiac output under a wide range of loading conditions and chronotropic states. Although this device is clearly preload dependent, it is capable of maintaining normal systemic pressures during conditions of severe left ventricular dysfunction and circulatory collapse.

Animals↗
PubMed1991

First-pass nuclear magnetic resonance imaging studies using gadolinium-DTPA in patients with coronary artery disease.

Nuclear magnetic resonance (NMR) imaging has been shown to accurately portray cardiac anatomy and function. To investigate the potential of NMR imaging for the assessment of coronary stenosis in patients with chest pain, ultrafast NMR imaging in conjunction with a T1 (longitudinal relaxation time) contrast agent was performed in 17 patients with chest pain who had undergone cardiac catheterization. These included 12 patients with significant coronary artery stenoses and 4 who underwent repeat NMR study after myocardial revascularization. Cardiac images at rest were obtained during rapid intravenous injection of gadolinium-DTPA (0.04 mM/kg). Electrocardiographic-gated images were acquired over 380 ms, with repetitive images obtained every 3 to 4 s. After contrast injection, there was pronounced signal enhancement in the right ventricular cavity, followed by enhancement in the left ventricular cavity and myocardium. Regional myocardium perfused by a diseased vessel demonstrated a lower peak signal intensity (p = 0.001) and lower rate of signal increase (p = 0.001) than did myocardium perfused by coronary arteries without stenosis. Repeat NMR study after revascularization showed an increase in peak signal intensity (p less than 0.002). These results demonstrate the clinical potential of dynamic gadolinium-DTPA-enhanced NMR imaging for the assessment of coronary artery disease in patients with chest pain. In combination with anatomic and functional NMR imaging, this technique has the potential to provide a comprehensive noninvasive cardiac evaluation of patients with suspected coronary artery disease.

Adult↗
PubMed1991

Regional diastolic mechanics of ischemic and nonischemic myocardium in the pig heart.

To assess the role of segmental dyssynchrony as a determinant of ischemic diastolic dysfunction, systolic and diastolic mechanics of ischemic and nonischemic myocardium were compared in the open chest pig heart (n = 7). Pacing tachycardia (1.8 x heart rate at rest) was imposed for 3 to 5 min in the presence of a single critical stenosis of the left anterior descending artery (demand ischemia, n = 7). After 30 min of recovery, the left anterior descending artery was totally occluded for 1.5 min in the same pigs (primary ischemia, n = 6). Both demand and primary ischemia increased left ventricular end-diastolic pressure and prolonged the time constant of left ventricular pressure decline. Percent systolic shortening of ischemic segments (perfused by the left anterior descending artery) decreased by 32% during demand ischemia and by 120% during primary ischemia, but that of nonischemic segments (perfused by the left circumflex artery) did not change significantly during either type of ischemia. During demand ischemia (but not during primary ischemia), left ventricular diastolic pressure increased relative to segment length so that a higher diastolic pressure was needed to stretch the ischemic segment to the same length (decreased distensibility). In nonischemic areas, diastolic pressure and segment length increased commensurately during both types of ischemia, indicating no change in diastolic distensibility. During demand ischemia, peak early diastolic lengthening rates increased in nonischemic segments but remained unchanged in ischemic segments. Diastolic segmental dyssynchrony developed during both types of ischemia, but was more pronounced during primary ischemia. Therefore, segmental dyssynchrony is unlikely to account for the rise in diastolic pressure relative to segment length seen during demand ischemia.

Animals↗
PubMed1991

Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force generation during systole.

We tested the hypothesis that intracellular Ca++ [( Ca++]i) overload underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy. Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease. The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and [Ca++]i was measured with the bioluminescent calcium indicator aequorin. In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components. At 38 degrees C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared develop, which produced a rise in end-diastolic [Ca++]i, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development. We also found that drugs with increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them. These results may explain why patients with hypertrophic cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophic cardiomyopathy.

Adult↗
PubMed1991

Consistency endangered by FASB-GASB (Financial Accounting Standards Board, Government Accounting Standards Board ) dispute.

The Financial Accounting Foundation's (FAF's) November 1989 decision to uphold the 1984 jurisdictional arrangement between the Financial Accounting Standards Board (FASB) and the Government Accounting Standards Board (GASB) leaves little doubt that the healthcare industry will now be subject to two sets of accounting standards. The FAF's decision created a distinction between the accounting practices of government-owned hospitals and non-hospital governmental entities and their adherence to standards set by FASB, GASB, and the American Institute of Certified Public Accountants. A governmental healthcare organization should carefully determine which accounting rules it follows and remain attentive to further GASB developments.

Accounting↗
PubMed1991

Prognosis in heart failure: is systolic or diastolic dysfunction more important?

The clinical syndrome of congestive heart failure can result from inadequate myocardial contraction (systolic myocardial failure), from pseudo-heart failure due to circulatory overload, or from failure of the ventricles to fill at low pressure (diastolic myocardial failure). The presence of systolic or diastolic heart failure is most precisely defined by an examination of left ventricular pressure-volume relations. Diastolic failure commonly coexists with systolic dysfunction. However, in many patients, diastolic dysfunction may exist alone or as the predominant physiologic disturbance. This is especially true in such common disease states as systemic hypertension and ischemic heart disease. Like systolic heart failure, diastolic failure results in significant morbidity and mortality. Diastolic heart failure may correlate better with prognosis for symptoms and survival than traditional indices of systolic function. The presence of predominantly diastolic dysfunction in large numbers of patients with the diagnosis of congestive heart failure has important therapeutic implications.

Diastole↗
PubMed1991

Therapeutic approaches affecting diastolic ventricular function.

The therapeutic approaches affecting diastolic ventricular function are conditional on underlying physiology, especially as it relates to calcium cycling, early relaxation and rapid filling abnormalities, atrial function, hemodynamics, the presence of hypertrophy, and neurohormonal milieu. A wide variety of treatment considerations are discussed, with particular attention to the management of cardiomyopathy characterized by pure or predominant diastolic failure (Table 1).

Cardiovascular Agents↗
PubMed1990

Post-extrasystolic potentiation and the force-frequency relationship: differential augmentation of myocardial contractility in working myocardium from patients with end-stage heart failure.

We studied post-extrasystolic potentiation (PESP) and frequency potentiation (FP) of human working myocardium isolated from the ventricles of 10 patients with end-stage heart failure (CHF) and 17 non-failing controls (CTL). The contractility index was peak isometric tension developed in vitro by trabeculae carneae (CTL n = 34, CHF n = 31); programmed electrical stimulation was used to initiate as well as alter the timing relationship of the contractile events. While holding constant the total number of contractions per unit of time, we compared the augmentation of contractile performance that occurred upon doubling the stimulation frequency (FP) to that of changing the stimulation pattern (PESP). In the CTL group we found that FP and PESP differed in their ability to augment cardiac contractile performance, PESP being more effective; 105 +/- 13% for PESP vs. 34 +/- 11% (mean +/- S.E.M.) for FP. In the CHF group, the inotropic response to PESP was similar to CTL; in contrast, the relative efficacy of FP (3 +/- 3%) compared to PESP (81 +/- 14%) was markedly diminished. Studies with positive inotropic agents revealed that the percent change in contractility induced by FP and PESP depends upon the relative inotropic state of the heart; however, the contractile response to PESP always equaled or exceeded those produced by clinically relevant concentrations of inotropic agents, particularly in CHF muscles. Agents that increase intracellular levels of adenosine 3',5'-cyclic monophosphate reversed the FP abnormalities seen in the CHF group, suggesting that deficient production of this second messenger in heart failure may cause the abnormal force-frequency relationship in failing myocardium. We conclude that the differential responses of myopathic muscle to PESP and FP may be caused by abnormal restitution processes during diastole. Our results suggest that PESP may be an effective therapeutic modality for patients with severe heart failure who have failed to adequately respond to inotropic drugs, and may serve as a useful indicator of cardiac contractile reserve in these patients.

Assisted Circulation↗
PubMed1990

Diastolic function and heart failure: an overview.

Diastolic dysfunction is being recognized increasingly as a primary cause of congestive heart failure. It may result from physiological abnormalities of myocardial relaxation, or anatomical abnormalities which increase resistance to ventricular inflow. With regard to physiological abnormalities, there is substantial evidence to indicate that myocardial ischaemia and hypertrophy are two conditions characterized by impaired inactivation and relaxation of myocardial cells. These conditions often co-exist in patients with idiopathic hypertrophic subaortic stenosis or calcific valvular aortic stenosis. Recent evidence also suggests a role for calcium overload in the diastolic dysfunction seen in some patients with advanced congestive heart failure. Diastolic dysfunction may be of fundamental importance in the pathophysiology of flash pulmonary oedema in patients with advanced ischaemic heart disease, since myocardial ischaemia in such patients may lead to a decline in relaxation rate, increased resistance to early diastolic filling and further impairment in diastolic coronary blood flow due to intramyocardial compression of capillaries and venules. During the transient ischaemia of angina pectoris, patients with multivessel coronary artery disease often show a striking upward shift in the left ventricular diastolic pressure-volume relationship, signifying a marked decrease in distensibility of the left ventricular chamber. With regard to anatomical abnormalities, diastolic dysfunction in heart failure may result from structural changes within the ventricular wall. Diastolic dysfunction of the left ventricle may result from extrinsic compression by pericardial effusion (tamponade), pericardial constriction, and right ventricular overload. Thus, a variety of physiological and anatomical abnormalities may lead to increased resistance to diastolic filling of one or both ventricles, resulting in diastolic heart failure.

Diastole↗