Biomedical subjects

W Grossman

Publications and source records attributed to W Grossman.

At least 37 records · Page 2Linked to original sources

PubMed1994

Basic FGF enhances endothelium-dependent relaxation of the collateral-perfused coronary microcirculation.

The effect of chronic, periadventitial administration of basic (b) fibroblast growth factor (FGF) on endothelial dysfunction in the collateral-dependent and normally perfused coronary microcirculation was examined. Ameroid constrictors were placed on the proximal left circumflex coronary artery (LCX) in 23 pigs. In 11 pigs, bFGF was released from calcium alginate microcapsules into the perivascular space of the proximal left anterior descending coronary artery (LAD) and LCX. After 5-8 wk, coronary arterial microvessels (80-170 microns) were studied in a pressurized (40 mmHg) no-flow state with video microscopy. Receptor-mediated endothelium-dependent relaxations to ADP and serotonin were reduced while contraction to acetylcholine was enhanced in the collateral-dependent LCX microvessels of non-bFGF-treated control hearts. Relaxation of vessels to the non-receptor-mediated, endothelium-dependent agent A-23187; endothelium-independent relaxation to nitroprusside; and contraction to KCl were similar in all groups. Chronic treatment with bFGF normalized responses to ADP, serotonin, and acetylcholine in the collateral-dependent LCX region but had no effect on the responses of vessels in the normally perfused LAD region. Arteriolar density in the collateral-perfused LCX region of bFGF-treated hearts was markedly increased (4-fold compared with that in untreated hearts, suggesting a link between the angiogenic effect of bFGF and its action on endothelial preservation. Thus the periadventitial, sustained delivery of bFGF preserves receptor-mediated, endothelium-dependent responses in the collateral-dependent LCX region but has no effect on responses of microvessels in the normally perfused LAD region or on non-receptor-mediated endothelium-dependent relaxation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1994

Acidemia and hypernatremia enhance postischemic recovery of excitation-contraction coupling.

The purpose of the present study was to determine whether Na(+)-H+ and Na(+)-Ca2+ exchanges modulate postischemic recovery of excitation-contraction coupling. Experiments were performed in 43 isolated isovolumic dog hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, paced at 2 Hz). A 3 x 3-mm region at the left ventricular (LV) apex was loaded with aequorin for monitoring [Ca2+]i simultaneously with LV pressure. No-flow ischemia for 2 to 3 minutes was followed by 20 minutes of aerobic reperfusion with (1) unmodified control blood (141 mmol/L Na+, pH 7.40), (2) acidemic blood (141 mmol/L Na+, pH 6.60, at 0 to 3 minutes of reperfusion), (3) hypernatremic blood (149 or 157 mmol/L Na+, pH 7.40, at 0 to 20 minutes of reperfusion), or (4) hyperosmotic blood (141 mmol/L Na+ + 30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediately followed by an increase in [Ca2+]i and LV systolic and diastolic pressure that persisted for 2 to 3 minutes before returning to or below baseline. Ventricular arrhythmia occurred during this period (> 80%). This transient increase of [Ca2+]i was attenuated by acidemic or hypernatremic perfusate. With acidemic or hypernatremic reperfusion, recovery of LV developed pressure at 20 minutes was more complete than with unmodified control reperfusion: acidemic blood (n = 7), 93 +/- 3% (P < .01); hypernatremic blood (149 mmol/L Na+, n = 7), 89 +/- 2% (P < .02); hypernatremic blood (157 mmol/L Na+, n = 4), 91 +/- 2% (P < .01); and unmodified control blood (n = 17), 80 +/- 2%. With hyperosmotic reperfusion, recovery of LV developed pressure at 20 minutes was not improved (82 +/- 3%). From these results we conclude that (1) an increase in intracellular Ca2+ occurs transiently after no-flow ischemia and may cause arrhythmia and decreased Ca2+ responsiveness of the contractile elements, (2) acidemic and hypernatremic reperfusion ameliorates postischemic dysfunction by preventing the increase in intracellular Ca2+, suggesting that (3) Na(+)-H+ and Na(+)-Ca2+ exchange may play important modulatory roles during reperfusion.

Animals↗

PubMed1994

Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.

The effect of basic fibroblast growth factor (bFGF) administration on regional myocardial function and blood flow in chronically ischemic hearts was studied in 26 pigs instrumented with proximal circumflex coronary artery (LCX) ameroid constrictors. In 13 animals bFGF was administered extraluminally to the proximal left anterior descending (LAD) and LCX arteries with heparin-alginate beads and 13 other animal served as controls. bFGF-treated pigs showed a fourfold reduction in left ventricular infarct size compared to untreated controls (infarct size: 1.2 +/- 0.4% vs. 5.1 +/- 1.3% of LV mass, mean +/- SEM, P < 0.05). Percent fractional shortening (% FS) in the LCX area at rest was reduced compared with the LAD region in both bFGF and control pigs. However, there was better recovery in the LCX area after rapid pacing in bFGF-treated pigs (% FSLCX/% FSLAD, 22.9 +/- 7.3%-->30.5 +/- 8.5%, P < 0.05 vs. prepacing) than in controls (16.0 +/- 7.8%-->14.3 +/- 7.0%, P = NS). Furthermore, LV end-diastolic pressure rise with rapid pacing was less in bFGF-treated than control pigs (pre-pacing; pacing; post-pacing, 10 +/- 1; 17 +/- 3; 11 +/- 1* mmHg vs 10 +/- 1; 24 +/- 4; 15 +/- 1 mmHg, *P < 0.05 vs. control). Coronary blood flow in the LCX territory (normalized for LAD flow) was also better during pacing in bFGF-treated pigs than in controls. Thus, periadventitial administration of bFGF in a gradual coronary occlusion model in pigs results in improvement of coronary flow and reduction in infarct size in the compromised territory as well as in prevention of pacing-induced hemodynamic deterioration.

Animals↗

PubMed1993

Atherectomy of the subclavian artery for patients with symptomatic coronary-subclavian steal syndrome.

OBJECTIVES: This study addresses the efficacy of directional atherectomy in the subclavian artery for the relief of angina in patients with the coronary-subclavian steal syndrome. In addition, we review the histologic findings from the atherectomy specimens. BACKGROUND: The coronary-subclavian steal syndrome may occur after internal mammary-coronary artery bypass grafting. It is due to a stenosis in the subclavian artery proximal to the origin of the internal mammary artery and causes frank ischemia to the area supplied by the graft. Currently, surgery is the corrective procedure of choice. METHODS: In three patients with severe subclavian artery stenoses and unstable angina, directional atherectomy was performed using a peripheral atherectomy catheter through a percutaneous femoral approach. The patients ranged from 43 to 71 years of age and had undergone internal mammary-coronary artery bypass grafting 3 to 10 years previously. Each patient had severe peripheral vascular and cerebrovascular disease. RESULTS: All three patients had immediate symptomatic relief after the atherectomy, and postprocedure exercise testing demonstrated improved cardiac function. Two patients remain asymptomatic at 7 and 8 months, respectively; the third patient developed unstable angina 9 months later because of severe restenosis that was again successfully treated with atherectomy. Histologic examination of the specimens revealed atherosclerotic plaque, occasionally with adventitia. The specimen from the repeat atherectomy showed severe intimal hyperplasia. CONCLUSIONS: Directional atherectomy appears to be a safe and effective treatment for coronary-subclavian steal syndrome. This procedure may be the treatment of choice for patients in whom a vascular bypass operation is not feasible.

Adult↗

PubMed1993

Diastolic dysfunction as a cause of heart failure.

Diastolic dysfunction is an important cause of symptoms in patients with various types of cardiac disease. Increased left ventricular diastolic pressure may lead to pulmonary congestion, even in the setting of normal left ventricular systolic function. Although the physiology of diastolic function is complex, left ventricular diastolic pressure may become elevated through one of three broad mechanisms. Abnormalities intrinsic to the left ventricle may include 1) impaired left ventricular relaxation, a finding that is common in most cardiac diseases and may be particularly important during ischemia; 2) increased left ventricular wall thickness relative to cavity volume, which will shift the diastolic pressure-volume relation such that the same volume is associated with a higher pressure; and 3) increased myocardial stiffness, which is thought to be associated with interstitial fibrosis or scar tissue formation. In addition, diastolic pressures may become elevated because of factors extrinsic to the left ventricle. These may include 1) increased central blood volume, which will increase left ventricular pressure without altering the left ventricular pressure-volume relation; and 2) ventricular interaction mediated by pericardial restraint, which may cause a parallel upward shift of the diastolic pressure-volume relation. Treatment of the factors extrinsic to the left ventricle tends to be much more successful than treating abnormalities that are intrinsic to the ventricle. Improved understanding of myocardial relaxation at the cellular level and delineation of the molecular regulation of myocyte hypertrophy and fibroblast proliferation may lead to new and innovative approaches to the treatment of heart failure.

Animals↗

PubMed1993

Effect of zatebradine on contractility, relaxation and coronary blood flow.

OBJECTIVES: The purpose of this study was to compare the effects of zatebradine on heart rate, contractility and relaxation with those of its structural analog verapamil. We used isoproterenol, a potent beta-agonist, to see how these effects were modulated by sympathetic activation. We also compared the effects of zatebradine and verapamil on coronary blood flow and coronary blood flow reserve. BACKGROUND: Zatebradine, previously called UL-FS 49, is a new bradycardic agent believed to act selectively at the sinoatrial node. METHODS: Isolated isovolumetric pig hearts were prepared and left ventricular pressure, its first derivative (dP/dt), tau and heart rate were measured both before and after administration of either 0.975 mg of zatebradine (Group I, n = 8) or 125 micrograms of verapamil (Group II, n = 8). After the effects of each drug reached a plateau, a continuous infusion of isoproterenol was started and measurements were obtained again and compared with a third group of measurements from control hearts infused with isoproterenol after receiving only saline solution (n = 8). We also assessed the effects of zatebradine and verapamil on coronary vascular tone by measuring flow in the left anterior descending coronary artery in intact anesthetized open chest pigs both before and after the intracoronary administration of these drugs (n = 8 for each). All preparations were atrially paced to negate any bradycardiac effects of the drugs. RESULTS: In the group that received zatebradine, mean (+/- SE) heart rate decreased from 143 +/- 8 to 99 +/- 4 beats/min (p < 0.01) and there was no significant change in either peak left ventricular systolic pressure, dP/dt or tau. In contrast, verapamil produced a lesser decrease in heart rate (136 +/- 7 to 120 +/- 7 beats/min, p < 0.05) but produced substantial decreases in peak left ventricular pressure (100 +/- 3 to 45 +/- 4 mm Hg, p < 0.01) and dP/dt (68% decrease, p < 0.01) and an increase in tau (+26%, p < 0.05). Isoproterenol restored these variables toward normal values in the hearts treated with verapamil, although left ventricular systolic pressure and dP/dt were restored to control values only at the highest isoproterenol concentrations. In the hearts treated with zatebradine, isoproterenol significantly increased left ventricular pressure and contractility and decreased tau; however, heart rate remained unchanged at peak effect. Zatebradine had no effect on coronary blood flow and there was a 100% increase in flow with reactive hyperemia. Conversely, verapamil increased coronary flow by 100%, with no subsequent further increase by reactive hyperemia compared with control values. CONCLUSIONS: Although structurally similar to verapamil, zatebradine is a highly specific bradycardic agent. It has little direct effect on left ventricular developed pressure, contractility, relaxation and coronary vascular tone. Furthermore, the bradycardic effect of zatebradine unlike that of verapamil, is not overcome by doses of isoproterenol that increase developed pressure and contractility and improve relaxation. Because of its highly specific bradycardic effect, this drug may potentially be useful in treating patients with ischemic heart disease or congestive heart failure.

Animals↗

PubMed1993

Relationship of abnormal intracellular calcium mobilisation to myocyte hypertrophy in human ventricular myocardium.

OBJECTIVE: Calcium transients in muscles from patients with end stage heart failure consist of two components (L1 and L2) at physiological extracellular calcium concentrations ([Ca2+]o); the second component (L2) can appear in normal human myocardium at high [Ca2+]o. In muscles from end stage heart failure patients L2 is associated with significant hypertrophy. To expand these observations a group of muscles from control patients with mild hypertrophy but without overt heart disease was studied (n = 8), in which a second calcium transient component was present during high [Ca2+]o. METHODS: Using the ratio of the two components of the calcium transient (L2/L1) seen in trabeculae from heart failure patients as a marker of intracellular calcium mobilisation, the hypothesis was tested that the extent of abnormality in transsarcolemmal calcium flux, and/or sarcoplasmic reticular calcium release and reuptake, correlates with the degree of hypertrophy present. RESULTS: In contrast to non-hypertrophied myocardium, hypertrophied myocardium from patients without heart failure often showed an increase in the L2/L1 ratio at higher [Ca2+]o. Hypertrophied myocardium from patients with failure showed a progressive increase in the L2/L1 ratio, reflecting further impairment of calcium mobilisation. There was a positive correlation between the degree of hypertrophy and calcium mobilisation alterations that was enhanced by raised [Ca2+]o. Altered [Ca2+]i mobilisation may develop early in the course of hypertrophy, before the onset of clinical signs of cardiac dysfunction.

Aequorin↗

PubMed1993

Left ventricular diastolic function in the normal and diseased heart. Perspectives for the anesthesiologist (1).

Attempts to quantitatively describe ventricular function during diastole have been stimulated by the recognition that diastolic mechanics significantly influence overall cardiac performance, and that diastolic dysfunction may precede, or substantially contribute to, abnormalities of systolic function in various pathologic conditions (table 1). Indices of diastolic function can be derived invasively or noninvasively, and focus on the measurement of a diverse and complex set of separate, but intimately interrelated, processes that, while complementary, may not be directly comparable. Measurement of these indices is complicated, because diastolic function depends on several determinants: active, energy-dependent forces (isovolumic ventricular relaxation); passive and dynamic filling characteristics (chamber and myocardial stiffness); and extrinsic factors (left atrial function, ventricular interaction, valvular integrity, pericardial restraint, and myocardial blood flow), as well as other conditions that affect myocardial function during systole (preload, afterload, heart rate, and inotropic state). The diversity of events occurring during diastole indicates that a single index of diastolic function cannot adequately describe this period of the cardiac cycle, and the physiologic implications of diastolic dysfunction may be different, depending on the period of diastole affected (table 1). Thus, assessment of diastolic function is complicated, because of the heterogeneity of the event and the multiple factors that influence it. Despite the inherent potential limitations of indices describing diastolic function, these parameters provide useful references for evaluating the natural history of patients with diastolic heart failure, for assessing the benefits of therapeutic interventions of anesthetic actions, and for enhancing our knowledge of cardiac pathophysiology.

Anesthesiology↗

PubMed1993

Left ventricular diastolic function in the normal and diseased heart. Perspectives for the anesthesiologist (2).

Several important questions remain to be answered by future research. First, it is unclear whether any abnormal index of diastolic function can be used to estimate disease severity, or to prognostically identify patients who will subsequently develop systolic abnormalities or frank left ventricular dysfunction. A temporal relationship between the appearance of diastolic dysfunction and ultimate left ventricular decompensation may, theoretically, exist, but such a relationship has yet to be established. Second, a growing body of evidence indicates that pharmacologic therapy with Ca2+ channel antagonists, beta-adrenergic agonists or antagonists, phosphodiesterase inhibitors, or angiotensin converting enzyme inhibitors may acutely or chronically benefit certain patients with diastolic dysfunction. Whether the impact of early recognition and therapeutic intervention in patients with diastolic dysfunction can be translated into an improvement of quality of life or enhanced survival remains unknown. Third, recent evidence indicates that fundamental changes in the biochemistry of the cardiac myocyte may represent a final common pathway for the development of congestive heart failure resulting from intrinsic cardiac disease. Altered expression of genes coding for the ATP-dependent Ca2+ pumps in the sarcolemma and the sarcoplasmic reticulum, regulatory proteins such as phospholamban, and the proteins composing the contractile apparatus have been identified that play critical roles in the pathophysiology of myocardial failure, and have important implications for potential pharmacologic therapy. Future research will more clearly elucidate these cellular and biochemical mechanisms of left ventricular failure. Lastly, although intravenous and inhalational anesthetics produce derangements in normal diastolic function to varying degrees, whether the effects of these agents on diastolic performance are exacerbated in disease processes manifested by abnormal diastolic mechanisms requires further evaluation.

Anesthetics↗

PubMed1993

Central retinal artery occlusion after scoliosis surgery with a horseshoe headrest. Case report and literature review.

Central retinal artery occlusion is a well-documented entity that occurs after trauma and embolic, thrombotic, or spasmodic episodes in both children and adults. Its occurrence as a complication of elective surgery is very rare but quite tragic. This report describes a case of central retinal artery occlusion occurring in a child after scoliosis surgery in which a horseshoe headrest was used. Recommendations are given on how to avoid this serious complication.

Blindness↗

PubMed1993

Survival after the onset of congestive heart failure in Framingham Heart Study subjects.

BACKGROUND: Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. METHODS AND RESULTS: Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 +/- 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/- 10.0 years in the 1980s; p < 0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). CONCLUSIONS: CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.

Age Factors↗

PubMed1993

Left ventricular diastolic chamber stiffness and intramyocardial coronary capacitance in isolated dog hearts.

BACKGROUND: Because the myocardium is perfused primarily during diastole, changes in diastolic properties of the left ventricle (LV) should influence the intramyocardial circulation. METHODS AND RESULTS: We examined the influence of LV diastolic properties on the magnitude and localization of intramyocardial coronary capacitance by analyzing the coronary pressure-venous flow relation in isolated, isovolumic dog heart preparations. After sudden occlusion of the left coronary artery during a long diastole, we measured precapacitance and postcapacitance resistances (RPRE and RPOST) and calculated intramyocardial coronary capacitance (CIM) from RPOST and the time constant of the coronary venous flow decay. Using this method, we characterized the effects of coronary vasodilation, LV diastolic volume, and LV diastolic chamber stiffness on the coronary circulation. The magnitude of CIM increased from 0.09 +/- 0.01 to 0.24 +/- 0.20 mL.mm Hg-1 x 100 g-1 (P < .01) after adenosine-induced vasodilation, whereas both RPOST and RPRE decreased significantly. The ratio of RPOST to RPRE+RPOST decreased from 0.35 +/- 0.02 to 0.23 +/- 0.02 (P < .01), suggesting redistribution of CIM to the distal portion of the coronary vascular tree. An increase in LV volume and wall stress was imposed to increase LV diastolic pressure from 2 +/- 0.1 to 25 +/- 1 mm Hg: this increased RPOST significantly but not RPRE and decreased the magnitude of CIM. The resistance ratio did not change significantly. Increased LV diastolic chamber stiffness induced by hypoxic perfusion (isovolumic LV diastolic pressure increased from 11 +/- 1 to 28 +/- 1 mm Hg) raised RPOST and decreased the magnitude of CIM from 0.32 +/- 0.12 to 0.17 +/- 0.04 mL.mm Hg-1 x 100 g-1 (P < .05). The resistance ratio increased significantly from 0.21 +/- 0.05 to 0.33 +/- 0.05 with increased LV diastolic chamber stiffness. Adjustment of LV diastolic volume to lower diastolic pressure to 10 +/- 1 mm Hg did not alter these changes significantly, suggesting that an intrinsic increase in myocardial stiffness played a major role in these changes. CONCLUSIONS: Extravascular compression by raised LV diastolic volume and/or increased LV diastolic chamber stiffness acted mainly on coronary vessels that determine intramyocardial capacitance and postcapacitance resistance.

Animals↗

PubMed1992

Predictors of long-term outcome after percutaneous balloon mitral valvuloplasty.

BACKGROUND: Percutaneous balloon mitral valvuloplasty is known to produce short-term hemodynamic and symptomatic improvement in many patients with mitral stenosis. Comprehensive assessment of the clinical usefulness of balloon valvuloplasty requires evaluation of patients' long-term outcomes. METHODS: We performed balloon mitral valvuloplasty in 146 patients between October 1, 1985, and October 1, 1991. Base-line demographic, clinical, echocardiographic, and hemodynamic variables were evaluated in order to identify predictors of long-term event-free survival. RESULTS: Balloon mitral valvuloplasty was completed successfully in 136 (93 percent) of the patients in whom the procedure was attempted; it resulted in an increase in the mean (+/- SD) mitral-valve area from 1.0 +/- 0.4 to 2.1 +/- 0.9 cm2 and a decrease in the mean transmitral pressure gradient from 14 +/- 5 to 6 +/- 3 mm Hg (P < 0.001 for both comparisons). The estimated overall five-year survival rate was 76 +/- 5 percent, and the estimated five-year event-free survival rate (the percentage of patients without mitral-valve replacement, repeat valvuloplasty, or death from cardiac causes) was 51 +/- 6 percent. According to multivariate Cox proportional-hazards analysis, the independent predictors of longer event-free survival were a lower mitral-valve echocardiographic score (a measure of mitral-valve deformity; range, 0 for a normal valve to 16 for a seriously deformed valve; P < 0.001), lower left ventricular end-diastolic pressure (P = 0.001), and a lower New York Heart Association (NYHA) functional class (P = 0.04). Patients with no risk factors for early restenosis or only one risk factor (echocardiographic score > 8, left ventricular end-diastolic pressure > 10 mm Hg, or NYHA functional class IV) had a predicted five-year event-free survival rate of 60 to 84 percent, whereas patients with two or three risk factors had a predicted five-year event-free survival rate of only 13 to 41 percent. CONCLUSIONS: Balloon mitral valvuloplasty as a treatment for selected patients with mitral stenosis has good long-term results. The long-term outcome after this procedure can be predicted on the basis of patients' base-line characteristics.

Catheterization↗

PubMed1992

Effects of endothelin on intracellular Ca2+ and contractility in single ventricular myocytes from the ferret and human.

We investigated the role of endothelin-1 on peak intracellular Ca2+ ([Ca2+]i) and peak shortening of ventricular myocytes (loaded with indo-1/AM) from failing human hearts. 10 nM of ET-1 significantly increased the cell peak shortening (84 +/- 29%, P less than 0.05) without significantly increasing the peak [Ca2+]i (15 +/- 7%, P greater than 0.05). Further studies on ferret cardiac myocytes indicated that in addition to producing dose-dependent (0.1-10 nM) significant increases in peak shortening (max 55 +/- 6% P less than 0.01) and non-significant increases in peak [Ca2+]i (max 35 +/- 19%, P greater than 0.05), endothelin-1 significantly shifted the peak [Ca2+]i-peak shortening curve upward. The results suggest that endothelin-1 acts directly on human and ferret cardiac myocytes to produce a positive inotropic effect that may predominantly be due to an enhanced myofilament Ca2+ responsiveness.

Adult↗

PubMed1992

Coronary arteriovenous fistula presenting as congestive heart failure.

Coronary arteriovenous fistulae are rare, but can be of hemodynamic significance. We report a circumflex-coronary sinus fistula in an elderly man which was associated with a loud continuous murmur and congestive heart failure. Noninvasive evaluation, including transesophageal echocardiography and magnetic resonance imaging, suggested the diagnosis. Angiographic diagnosis of concomitant atherosclerotic coronary disease may be difficult, and can require postoperative study.

Aged↗

PubMed1992

Responsiveness of the myofilaments to Ca2+ in human heart failure: implications for Ca2+ and force regulation.

Myofilament calcium sensitivity and maximal calcium-activated force are fundamental properties of the contractile proteins in the heart. We examined these properties in normal human right-ventricular trabeculae carneae obtained from hearts of brain-dead patients with no known cardiac disease, and from patients with end-stage heart failure undergoing cardiac transplantation. There were no differences in calcium-activation of the control and myopathic muscles from chemically-skinned trabeculae or from intact tetanized preparations. We then tested the effect of DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole - carbonitrile), a new inotropic agent, in both preparations. In myopathic muscles, 1 microM DPI sensitized the myofilaments to Ca2+, as evidenced by a significant shift of the [Ca2+]-force relationship towards lower [Ca2+], in both skinned and intact preparations. On the other hand, the same concentration of DPI did not affect the calcium-activation in control muscles in both preparations. We also found that the twitch [Ca2+]-force relationship, which has been used as an indication of myofilament sensitivity, was dissociated from the steady-state [Ca2+]-force relationship, and was shifted along the [Ca2+] axis by modulation in the time-course of the twitch and [Ca2+]i, and not by the sensitivity of the myofilaments to Ca2+. Protein kinase C stimulation differentially altered the responsiveness of the myofilaments to Ca2+ in normal and myopathic muscle fibers. We propose that even though calcium activation and maximal calcium-activated force are unaltered in myopathic hearts there are changes in thin filament regulation in myopathic hearts that result in altered responses to agents that directly act on the thin filaments, and that the potential for force development is similar in normal and myopathic human hearts.

Actin Cytoskeleton↗

PubMed1992

The use of freeze-dried fibular allograft in anterior cervical fusion.

Eighty-three segmental fusions were performed on 42 patients who underwent anterior cervical discectomy and fusion with freeze-dried fibular allograft for cervical spondylosis. Fusions were carried out over one to four levels. The mean follow-up period was 22.1 months (range, 9-47 months). The patients had both clinical and radiographic follow-up. Eighty-eight percent of the patients were found to have excellent or good clinical results. Radiographic follow-up revealed that 92% of the grafts obtained complete or partial union by 6 months after surgery. Forty patients were shown to be radiographically stable on lateral flexion and extension films by 8 weeks after surgery. The use of freeze-dried fibular allograft is a safe and efficacious procedure.

Bone Transplantation↗

PubMed1992

Endothelial modulation of porcine coronary microcirculation perfused via immature collaterals.

Porcine hearts have relatively few native collateral vessels and lack the propensity to develop normal perfusion to the collateral-dependent myocardium. To examine microvascular responses in the collateral-dependent region, collateral vessels were stimulated in pigs by the Ameroid constrictor technique. After 4-7 wk, isolated microarterial vessels (90-170 microns ID) were studied in a pressurized (40 mmHg), no-flow state. Microvessels from noninstrumented pigs were used as controls for vascular studies. Although myocardium in the collateral-dependent region showed minimal evidence of infarction, percent systolic shortening was reduced at rest and after pacing compared with myocardium in the normally perfused region. Relaxations to the receptor-mediated endothelium-dependent agents ADP and bradykinin were impaired in collateral-dependent coronary microvessels. Relaxations to the calcium ionophore A23187, which acts through a non-receptor-mediated mechanism, were similar in control and Ameroid microvessels. Relaxations to the endothelium-independent agent sodium nitroprusside were markedly enhanced in microvessels from the collateral-dependent region compared with microvessels from control hearts. In conclusion, receptor-mediated endothelium-dependent relaxation is impaired and endothelium-independent relaxation to sodium nitroprusside is enhanced in microvessels from myocardium perfused by immature collateral vessels.

Animals↗