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Biomedical subjects

B H Lorell

Publications and source records attributed to B H Lorell.

At least 73 records · Page 4Linked to original sources
PubMed1991

Localization and regulation of c-fos and c-jun protooncogene induction by systolic wall stress in normal and hypertrophied rat hearts.

The effect of changes in left ventricular (LV) systolic force generation on cardiac c-fos and c-jun protooncogene expression was studied by using isolated beating hearts from male Wistar rats. An isovolumic buffer-perfused heart preparation was utilized in which coronary flow and heart rate were held constant and increments in LV balloon volume were used to generate defined levels of LV systolic wall stress. Using Northern and slot-blot analyses, we found that LV tissue from control hearts that generated high levels of LV systolic wall stress expressed 3- to 4.4-fold higher c-fos and c-jun mRNA levels in comparison with tissue from the respective flaccid right ventricles, and in comparison with LV tissue from hearts that generated minimal LV systolic wall stress. To distinguish the role of passive LV diastolic wall stretch from active LV force generation, we found that distension of the LV balloon per se did not have a significant effect on protooncogene induction in hearts perfused with 2,3-butanedione monoxime, which prevents systolic cross-bridge cycling and force generation. In additional hearts studied at a constant LV balloon volume to generate an LV end-diastolic pressure of 10 mm Hg, c-fos mRNA levels were proportional to the magnitude of peak LV systolic wall stress (r = 0.823, P less than 0.05). In these protocols, Fos protein was localized by immunohistochemistry in myocyte nuclei with minimal staining in fibroblasts and vascular smooth muscle. When c-fos and c-jun mRNA expression was compared in hearts with chronic LV hypertrophy due to ascending aortic banding and age-matched control hearts that generated similar incremental levels of LV systolic wall stress, significantly lower levels of c-fos and c-jun mRNA were measured in the hypertrophied hearts. However, there was no difference in protooncogene mRNA expression in response to stimulation by the Ca2+ ionophore A23187. These data suggest that, in this isolated isovolumic beating heart preparation, the active generation of an acute increment in LV systolic force independent of passive diastolic myocardial stretch causes a rapid induction of both c-fos and c-jun, which is down-regulated in the presence of established LV hypertrophy.

Animals↗
PubMed1991

Salvage of branch vessels during bifurcation lesion angioplasty: acute and long-term follow-up.

To evaluate angiographic success, frequency of branch vessel loss and salvage, and long-term outcome, we studied the early and late outcomes of 56 consecutive patients who underwent PTCA of bifurcation lesions, which involved the left anterior descending or left circumflex coronary artery, with stenoses greater than 70% in both the parent and an involved branch vessel. In 35 patients (63%), the PTCA strategy was attempted dilation of both the main vessel and the involved branch vessels using predominantly a double-wire, sequential balloon technique; in 21 (27%) the PTCA attempt was confined to the main vessel alone. Transient angiographic occlusion of the branch vessel occurred in 32% of patients in whom dilation of both vessels was attempted, and in 38% in whom the main vessel alone was dilated (p = NS); 91% of the occluded branch vessels were the salvaged when sequential angioplasty of both vessels had been initially planned, compared to only 38% when the initial strategy had been dilation of the main vessel alone (p less than .05). Predischarge exercise testing showed residual ischemia in 6% of patients who had both vessels successfully dilated, versus 37% in those in whom dilatation was confined to the main vessels (p less than .01). Clinical restenosis, defined as late (greater than 6 weeks) recurrence of angina or a positive exercise test, occurred in 42% of patients who had both vessels successfully dilated. Thus although bifurcation lesion angioplasty frequently results in transient branch vessel loss, these branches can usually be salvaged using a double-wire technique but tend to have a higher late restenosis than conventional single vessel PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1991

A new technique for sheathless percutaneous intraaortic balloon catheter insertion.

Intraaortic balloon counterpulsation is helpful for controlling myocardial ischemia and providing hemodynamic support, but its applicability is limited by lower extremity ischemic complications in a significant percentage of patients. We developed a new sheathless technique for percutaneous intraaortic balloon catheter insertion which reduces the effective catheter diameter. A pilot study using this new technique resulted in a 10% rate of limb ischemia, without compromise of balloon function. We conclude that this technique may be useful in reducing the incidence of limb ischemia associated with intraaortic balloon counterpulsation.

Aged↗
PubMed1991

Implications of echocardiographically assisted diagnosis of pericardial tamponade in contemporary medical patients: detection before hemodynamic embarrassment.

Identification of suspected pericardial tamponade and the decision to perform invasive drainage of the pericardial space have historically been based on classic bedside findings. Two-dimensional echocardiography has improved detection of pericardial effusion, but it may be excessively sensitive in evaluation of patients for hemodynamic embarrassment. Therefore, 50 consecutive medical patients were examined who were identified by echocardiography to have probable tamponade (defined as the presence of right heart chamber collapse in the presence of a pericardial effusion) and who underwent combined right-sided cardiac catheterization and percutaneous pericardiocentesis. All patients had elevated pericardial pressure. However, many had minimal evidence of hemodynamic compromise (94% had systolic blood pressure greater than or equal to 100 mm Hg and 58% had a cardiac index greater than or equal to 2.3 liters/min per m2). Pericardiocentesis resulted in hemodynamic improvement, but frequently did not alleviate dyspnea or correct tachycardia. Patients with malignancy as the cause of tamponade had a high mortality rate (the cumulative probability of survival in such patients was only 17% at 1 year). Echocardiographically assisted diagnosis of pericardial tamponade in medical patients results in the identification of a substantial subset of patients with only subtle evidence of hemodynamic compromise. This subset of patients differs sharply from medical patients described in previous reports with classic tamponade. Although the patients can be managed by invasive catheter pericardiocentesis with few complications, the natural history and the optimal management strategy for this group are not resolved.

Cardiac Catheterization↗
PubMed1991

Significance of diastolic dysfunction of the heart.

Diastolic dysfunction is an important cause of the clinical syndrome of congestive heart failure. Traditionally, the syndrome of pulmonary congestion due to the elevation of left heart filling pressure has been attributed to the depressed ability of the heart to eject blood during systole, with a secondary increase in left ventricular volume. However, heart failure can also occur when the left ventricle fails to receive blood during diastole at low filling pressures. With a mild degree of resistance of the left ventricle to diastolic filling, the initial hemodynamic manifestation may just be the elevation of left ventricular diastolic pressure and pulmonary venous pressure. More severe resistance to left ventricular filling may cause an inadequate extent of diastolic filling and insufficient myofiber stretch, which results in the depression of stroke volume. In this review, the factors contributing to diastolic dysfunction are discussed, with a particular focus on the role of diastolic heart failure in patients with ischemic heart disease or hypertrophy.

Animals↗
PubMed1990

Diastolic function in left ventricular hypertrophy: clinical and experimental relationships.

The evaluation of patients with left ventricular hypertrophy and the clinical syndrome of congestive heart failure requires the ability to distinguish between the etiologies of abnormal systolic contractile function and abnormalities of diastolic relaxation and filling. In patients with left ventricular hypertrophy and congestive heart failure, predominant diastolic dysfunction should be suspected when elevation of left ventricular diastolic pressure is detected in the presence of normal diastolic chamber volume or dimensions and preserved systolic shortening. The mechanisms which account for diastolic dysfunction in the presence of cardiac hypertrophy are controversial and are likely to be multiple. These mechanisms may include changes in left ventricular geometry, per se, changes in the composition of the left ventricular wall (fibrosis or alteration in collagen), and dynamic factors which modulate diastolic force inactivation (loading conditions, cytosolic calcium handling, cyclic AMP availability). In addition, recent studies suggest that hypertrophied cardiac muscle may be particularly susceptible to develop diastolic dysfunction in response to the stress of hypoxia or ischaemia.

Cardiac Volume↗
PubMed1990

Influence of glucose and insulin on the exaggerated diastolic and systolic dysfunction of hypertrophied rat hearts during hypoxia.

Myocardial hypertrophy can result in increased sensitivity toward the development of mechanical dysfunction during hypoxia. Alterations in glycolytic metabolism may contribute to this. We studied the response to 15 minutes of hypoxia in hypertrophied (deoxycorticosterone-salt hypertension model) and nonhypertrophied rat hearts and examined the influence of a high glucose (27.5 mM) and insulin (100 mU/ml) concentration. In response to hypoxia in the presence of a normal glucose concentration (5.5 mM), left ventricular end-diastolic pressure was higher in hypertrophied than in nonhypertrophied hearts (65 +/- 6 vs. 44 +/- 4 mm Hg; p less than 0.05). Perfusion with high glucose and insulin blunted the rise in left ventricular end-diastolic pressure in both hypertrophied and nonhypertrophied hearts and abolished the difference in diastolic dysfunction between groups during hypoxia (26 +/- 2 vs. 32 +/- 4 mm Hg, respectively; p = NS). At end hypoxia in the presence of a normal glucose concentration, developed pressure was more depressed in hypertrophied than in nonhypertrophied hearts (11 +/- 1 vs. 18 +/- 1% of baseline, respectively; p less than 0.05). Perfusion with high glucose and insulin resulted in improved function in both groups during hypoxia such that a greater impairment of developed pressure was no longer present in the hypertrophied versus nonhypertrophied hearts (21 +/- 1 vs. 24 +/- 2% of baseline, respectively; p = NS). At the end of hypoxic perfusion in the presence of a normal glucose concentration, hypertrophied hearts were producing 38% less lactate than nonhypertrophied hearts. Perfusion with high glucose and insulin increased lactate production in both groups and equalized lactate production between groups. Thus, the greater deterioration in hemodynamic function in hypertrophied hearts compared with nonhypertrophied hearts during hypoxia is associated with lower lactate production. Both the exaggerated hemodynamic dysfunction and deficient lactate production can be ameliorated by perfusion with a high glucose concentration and insulin.

Animals↗
PubMed1990

Contribution of endothelial cells to calcium-dependent fluorescence transients in rabbit hearts loaded with indo 1.

In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluorescence of the left ventricle during continuous excitation at 360 nm. In cells containing indo 1, an increase in [Ca2+]i is associated with an increase in fluorescence intensity at 400 nm, a decrease in intensity at 500 nm, and an increase in the 400:500 nm ratio. Beat-to-beat fluorescence transients were recorded from the surface of the heart coincident with contraction, indicating that a component of the fluorescence signals is derived from beating myocytes. To evaluate the potential contribution of endothelial cells, we compared the response to increases in [Ca2+]o or bradykinin (10(-5) M). In response to an increase of the [Ca2+] in the perfusate from 0.6 to 3.0 mM, left ventricular developed pressure and +dP/dt increased with a simultaneous increase in the [Ca2+]i-sensitive 400:500 nm ratio. Perfusion with the endothelial cell agonist bradykinin caused no change in left ventricular isovolumic peak systolic pressure or left ventricular dP/dt, whereas bradykinin evoked an immediate elevation in both the diastolic and systolic levels of the [Ca2+]i-sensitive 400:500 nm ratio. In additional experiments with indo 1-loaded isolated beating myocytes, superfusion with bradykinin had no effect on either the fluorescence [Ca2+]i transients or contractility. In contrast, superfusion of indo 1-loaded cultured endothelial cells with bradykinin caused the elevation of [Ca2+]i within seconds. Fluorescence microscopy of unstained frozen tissue sections from indo 1-loaded hearts also suggested the presence of more intense microvascular endothelial cell indo 1 fluorescence relative to that observed in myocytes. These experiments provide evidence that a component of [Ca2+]i-sensitive fluorescence of whole hearts loaded with indo 1 is contributed by nonmyocyte sources, including endothelial cells. These results also raise the caution that the abrupt rise of [Ca2+]i that has been observed during the initial phase of ischemia in whole hearts loaded with indo 1 may be partly derived from endothelial cells rather than myocytes.

Animals↗
PubMed1990

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10(-8) M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3 +/- 4.1% vs 6.8 +/- 1.3%, P less than 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls.

Angiotensin I↗
PubMed1989

Use of pulmonary capillary wedge aspirates for the antemortem diagnosis of pulmonary microvascular tumor.

The diagnosis of pulmonary lymphangitic carcinoma usually requires fiberoptic bronchoscopy with transbronchial biopsy, percutaneous needle aspiration of the lung, and/or open lung biopsy. We performed right heart catheterization in three patients with adenocarcinoma, in whom the diagnosis of pulmonary lymphangitic carcinoma was made on the basis of cytologic examination of pulmonary capillary blood.

Adenocarcinoma↗
PubMed1989

The challenge of cardiomyopathy.

The combined clinical and pathophysiologic characteristics and diagnostic features as well as current concepts of pathogenesis, therapy and prevention of the principal forms of cardiomyopathy are reviewed. These include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy and specific cardiac muscle disease. Emphasis is placed on recent developments and unresolved questions requiring application of newer techniques of molecular biology and genetics and adult myocyte culturing.

Cardiomyopathy, Dilated↗
PubMed1989

Deleterious effect of ouabain on myocardial function during hypoxia.

The effect of cardiac glycosides on myocardial function during hypoxia is controversial. Accordingly, we studied left ventricular performance during hypoxia and reoxygenation in the presence of a mildly inotropic, nontoxic dose of ouabain using isolated, isovolumic, buffer-perfused rabbit hearts. After 15 min of hypoxia, left ventricular developed pressure was less in the ouabain-treated group than in controls (35 +/- 4 vs. 55 +/- 3 mmHg, P less than 0.025). Left ventricular end-diastolic pressure (LVEDP) increased more during hypoxia in the presence of ouabain (9 +/- 1 to 32 +/- 7 with ouabain vs. 9 +/- 1 to 14 +/- 3 mmHg without ouabain, P less than 0.005) despite comparable degrees of coronary vasodilatation and myocardial lactate production in the two groups. When coronary flow was abruptly reduced to zero to eliminate the coronary turgor contribution to diastolic pressure, LVEDP after 15 min of hypoxia in the presence of ouabain was greater than that in control hearts that did not receive ouabain (13 +/- 4 vs. 4 +/- 1 mmHg, P less than 0.05), implicating greater diastolic myocardial fiber tension in the ouabain group during hypoxia. With reoxygenation, recovery of developed pressure was less and end-diastolic pressure remained elevated in the ouabain-treated group when compared with controls. We conclude that a modestly inotropic dose of ouabain exacerbates the decrease in diastolic ventricular distensibility induced by hypoxia, worsens the decline in developed pressure during hypoxia, and impairs recovery during reoxygenation.

Animals↗
PubMed1989

Influence of hypertension with minimal hypertrophy on diastolic function during demand ischemia.

Hearts with advanced pressure-overload hypertrophy from systemic hypertension have been shown to have an increased susceptibility to the development of diastolic dysfunction in response to tissue hypoxia and ischemia. It is not known if this propensity to develop diastolic dysfunction in response to ischemia is dependent on the presence of a substantial increase in left ventricular mass, or alternatively, is characteristic of hearts subjected to mild chronic hypertension early in the development of cardiac hypertrophy. We tested the hypothesis that systemic hypertension associated with mild left ventricular hypertrophy increases the susceptibility to the development of diastolic dysfunction in response to demand ischemia. The effects of demand ischemia (6 minutes) were studied in hearts from New Zealand white rabbits with chronic systemic hypertension produced by the one-kidney, one-wrap method (n = 15) and compared with age-matched, sham-operated control rabbits (n = 11) with similar left ventricular mass (5.4 +/- 0.2 vs. 5.4 +/- 0.3 g, respectively). The hearts were studied using an isolated, isovolumic (balloon in left ventricle) preparation with absent pericardium that was perfused with fresh whole blood. At baseline, coronary perfusion pressure was 100 mm Hg with comparable coronary flow per gram left ventricular weight; the hearts were paced at a physiological rate of 3 Hz, and the left ventricular balloon volume was adjusted to achieve a left ventricular end-diastolic pressure of 15 mm Hg in both groups. Left ventricular balloon volume was similar in both groups and volume was thereafter held constant. At baseline, left ventricular systolic pressure (114 +/- 4 vs. 95 +/- 3 mm Hg, p less than 0.001) and developed pressure (18.9 +/- 1.2 vs. 15.1 +/- 0.9 mm Hg/g, p less than 0.05) were higher in the hearts from the hypertensive group in comparison with the control group. During the first minute of global ischemia produced by reducing coronary perfusion pressure from 100 to 20 mm Hg, there was an immediate fall in left ventricular systolic pressure in both groups without an increase in diastolic pressure. In response to the superimposition of pacing tachycardia (heart rate, 6 Hz) during the remaining 5 minutes of the period of ischemia, left ventricular developed pressure was comparable. However, isovolumic left ventricular end-diastolic pressure (measured during long diastoles obtained with transient cessation of pacing) rose to a significantly higher level in the hearts from hypertensive rabbits than in those from the control rabbits (29 +/- 3 vs. 18 +/- 2 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Contrast effects of isoproterenol and ouabain on left ventricular diastolic relaxation dysfunction in isolated, blood-perfused rabbit hearts.

We studied the influence of inotropic agents on prompt and transient left ventricular (LV) diastolic relaxation dysfunction produced by superimposition of pacing tachycardia on low-flow ischemia, using an isolated, blood-perfused and isovolumic (balloon-in-LV) rabbit heart preparation. The LV balloon volume was adjusted to produce an LV end-diastolic pressure (EDP) of 15 mmHg and was held constant thereafter. Coronary perfusion pressure was adjusted to 100 mmHg during baseline and to 20 mmHg during low-flow ischemia of 6 min. At baseline, isoproterenol and ouabain were administered to cause moderate and similar rises (14 +/- 3 and 16 +/- 4% above baseline values, respectively) in maximum + dp/dt of LVP with no change in LVEDP. In control hearts which received no drug, superimposition of 5-min pacing tachycardia on low-flow ischemia produced a significant and transient increase in LVEDP under constant LV volume (from 13.4 +/- 0.4 to 24.7 +/- 3.3 mmHg, p less than 0.01). In the hearts which received isoproterenol it did not change LVEDP (from 14.0 +/- 0.4 to 16.2 +/- 1.0 mmHg, NS). In contrast, the ouabain hearts showed a further increase in LVEDP (from 13.7 +/- 0.8 to 29.9 +/- 4.6 mmHg, p less than 0.01). LV developed pressure, myocardial oxygen consumption or myocardial lactate production during pacing tachycardia superimposed on the low-flow ischemia did not differ significantly among the 3 groups. Thus, isoproterenol markedly improved transient LV relaxation dysfunction produced by superimposition of pacing tachycardia on low-flow ischemia, in which an equipotent inotropic dose of ouabain exaggerated the relaxation dysfunction. These results suggest that calcium overload rather than ATP depletion per se contributes to transiently impaired diastolic relaxation by pacing tachycardia and low-flow ischemia.

Animals↗
PubMed1988

Use of percutaneous transluminal coronary angioplasty and bypass surgery despite improved medical therapy for unstable angina pectoris.

To evaluate current strategies for the management of unstable angina, 104 consecutive patients admitted to the coronary care unit with unstable angina during a 6-month period were followed prospectively. Although 58 patients had symptomatic relief with the initiation of intensive medical therapy, 46 (44%) continued to have episodes of angina despite maximal tolerated triple-drug antianginal therapy as well as aspirin or heparin, or both. In-hospital mortality for the 104 patients was 4%. The incidence of myocardial infarction was 8%, and differed (p less than 0.01) for the medically responsive group (3%) vs the medically refractory group (13%). Based on clinical status and coronary anatomy, patients were referred for either bypass surgery (46%), coronary angioplasty (41%) or continued medical therapy (13%). Choice of therapy varied according to the extent of coronary disease, with coronary angioplasty attempted in 72% of patients with 1-vessel disease, 44% of patients with 2-vessel disease and 7% of patients with 3-vessel disease. Angioplasty was performed with an initial success rate of 88%, and compared favorably with bypass surgery in terms of in-hospital mortality (0 vs 11%), late mortality (2.8 vs 7.7%), freedom from angina (62 vs 69%) and subsequent employment (44 vs 27%) at 18 months follow-up. The favorable results of angioplasty in this prospective observational study suggest that additional randomized trials should be conducted in this important patient group.

Adrenergic beta-Antagonists↗
PubMed1988

Diastolic function in patients with aortic stenosis: influence of left ventricular load reduction.

Pressure overload hypertrophy of the left ventricle due to aortic stenosis is associated with abnormalities of left ventricular isovolumic relaxation and early diastolic filling. The relative contribution of the hemodynamic load on the left ventricle to the impairment of diastolic function observed in this disorder remains poorly understood. To study this relation, the vasodilator nitroprusside was administered to eight patients with aortic stenosis and normal systolic function. The effect of a short-term reduction in left ventricular preload and afterload on left ventricular isovolumic relaxation and early diastolic filling was assessed by analysis of simultaneous micromanometer left ventricular pressure and radionuclide angiographic volume measurements. At baseline, left ventricular systolic and end-diastolic pressures were markedly elevated, and associated with prolongation of the time constant of left ventricular relaxation and depression of the left ventricular peak filling rate. Infusion of nitroprusside resulted in reduction of left ventricular systolic (204 +/- 31 to 176 +/- 31 mm Hg, p less than 0.05) and end-diastolic (31 +/- 8 to 18 +/- 6 mm Hg, p less than 0.05) pressures, with no associated improvement in time constant of left ventricular pressure decay (T) (68 +/- 25 to 80 +/- 37 ms, p = NS), T 1/2 (34 +/- 8 to 34 +/- 14 ms, p = NS), left ventricular peak filling rate (2.3 +/- 0.5 to 2.3 +/- 0.8 end-diastolic volume/s, p = NS) or time to left ventricular peak filling rate (150 +/- 50 to 144 +/- 37 ms, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

The physiological basis of left ventricular diastolic dysfunction.

Overall cardiac pump function requires adequate ventricular diastolic filling as well as normal systolic ejection. Abnormalities of the rate or extent of myocardial relaxation (diastolic dysfunction) have been described in a large variety of clinical conditions, including hypertrophy, ischemia, and after cardiac surgery. Diastolic and systolic dysfunction can be readily distinguished by analysis of pressure volume loops and utilization of echocardiography or nuclear cardiology gated blood pool scans. The mechanisms by which diastolic dysfunction can occur may be structural (hypertrophy, fibrosis) or dynamic (hypoxia, ischemia, alteration of diastolic cytosolic calcium levels). Hypertrophied myocardium is particularly susceptible to diastolic dysfunction by virtue of both structural changes (increased LV mass and interstitial fibrosis) and greater susceptibility to develop impaired myocardial relaxation during hypoxia or ischemia than nonhypertrophied myocardium.

Cardiomegaly↗