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.

Time course of left ventricular dilation after myocardial infarction: influence of infarct-related artery and success of coronary thrombolysis.

Dilation of the left ventricle after myocardial infarction is common, occurs rapidly (within 2 weeks of infarction) and may be self-limited. To evaluate the time course of postinfarction left ventricular dilation and to assess the impact of successful coronary thrombolysis, serial radionuclide left ventricular volume analyses were performed in 36 patients undergoing attempted thrombolysis for acute transmural myocardial infarction. All patients underwent cardiac catheterization, coronary angiography and attempted thrombolysis within 7 h of the onset of symptoms. The site of coronary occlusion was the left anterior descending coronary artery in 17 patients, the right coronary artery in 18 and, in 1 patient, occluded bypass grafts to the right and left circumflex coronary arteries. Attempted reperfusion using a thrombolytic agent was successful in 22 individuals, occurring 5 +/- 1 h after the onset of symptoms. Gated radionuclide ventriculography was performed early (mean time 1 day after admission, n = 36), subacutely (mean time 11 days postinfarction, n = 36) and late after infarction (mean time 10.5 months, n = 25), and a geometric technique was used to measure serial left ventricular end-diastolic volume. Left ventricular end-diastolic volume for the entire group increased significantly (p less than 0.01) from 153 +/- 30 ml at baseline to 172 +/- 45 ml (at 11 days) to 220 +/- 63 ml (at 10.5 months). Twenty of 36 patients showed greater than 20% increase in left ventricular end-diastolic volume (dilation) with time. This appeared early in seven patients, occurred remote from infarction in seven others and showed a progressive pattern in six.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Balloon dilation of mitral stenosis in adult patients: postmortem and percutaneous mitral valvuloplasty studies.

Preliminary reports have documented the utility of percutaneous balloon valvuloplasty of the mitral valve in adult patients with mitral stenosis, but the mechanism of successful valve dilation and the effect of mitral valvuloplasty on cardiac performance have not been studied in detail. Accordingly, mitral valvuloplasty was performed in five postmortem specimens and in 18 adult patients with rheumatic mitral stenosis, using either one (25 mm) or two (18 and 20 mm) dilation balloons. Postmortem balloon dilation resulted in increased valve orifice area in all five postmortem specimens, secondary to separation of fused commissures and fracture of nodular calcium within the mitral leaflets. In no case did balloon dilation result in tearing of valve leaflets, disruption of the mitral ring or liberation of potentially embolic debris. Percutaneous mitral valvuloplasty in 18 patients with severe mitral stenosis (including 9 with a heavily calcified valve) resulted in an increase in cardiac output (4.3 +/- 1.1 to 5.1 +/- 1.5 liters/min, p less than 0.01) and mitral valve area (0.9 +/- 0.2 to 1.6 +/- 0.4 cm2, p less than 0.0001), and a decrease in mean mitral pressure gradient (15 +/- 5 to 9 +/- 4 mm Hg, p less than 0.0001), pulmonary capillary wedge pressure (23 +/- 7 to 18 +/- 7 mm Hg, p less than 0.0001) and mean pulmonary artery pressure (36 +/- 12 to 33 +/- 12 mm Hg, p less than 0.01). Left ventriculography before and after valvuloplasty in 14 of the 18 patients showed a mild (less than or equal to 1+) increase in mitral regurgitation in five patients and no change in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS)

Mannitol.

Mannitol is an osmotic diuretic with properties that suit it to a variety of clinical situations. Despite the paucity of controlled studies that precisely define optimal use, a consensus based on published work and clinical experience may be reached. Mannitol can be used prophylactically, as a diagnostic aid, or as therapy for the oliguric state. The diuretic properties of mannitol are also useful in patients with refractory edema or intoxications by aspirin, barbiturates, or bromide. As an extracellular solute, the drug may ameliorate intracranial hypertension or symptoms of dialysis dysequilibrium. The renal and systemic effects of this versatile agent are discussed.

Recovery from rapidly progressive glomerulonephritis. Improvement after plasmapheresis and immunosuppression.

Two patients with rapidly advancing renal insufficiency underwent biopsy and were found to have crescentic glomerulonephritis. Patient 1 demonstrated findings compatible with Goodpasture's syndrome. Crescents were present in 100% of his glomeruli. Patient 2 had findings of immune complex-mediated glomerulonephritis and crescents in greater than 90% of his glomeruli. Both patients were treated with high-dose prednisone, cyclophosphamide, and plasmapheresis. Patient 2 additionally required hemodialysis for a brief period. Renal function improved in both patients and has not deteriorated after follow-up of 14 and 18 months, respectively. Repeated renal biopsies were performed in each patient. Our findings suggest that clinical improvement and histologic healing are possible in rapidly progressive glomerulonephritis despite the initial presence of crescents in every glomerulus.

Treatment of alkalosis with ammonium chloride: a case report.

Coma due to ammonium chloride used in the treatment of severe metabolic alkalosis is reported in a patient with normal hepatic and renal function. All symptoms resolved following discontinuance. Ammonium chloride should be abandoned as a treatment for metabolic alkalosis.

Renal hemodynamic changes during long-term antihypertensive therapy.

Studies of renal hemodynamics were carried out in 84 patients with essential hypertension during long-term antihypertensive therapy with a number of drugs. Renal perfusion was maintained or enhanced despite a fall in mean arterial pressure during therapy with hydrochlorothiazide, furosemide, clonidine, prazosin, and the combination of guanabenz and hydrochlorothiazide. Renal perfusion deteriorated during long-term treatment with propranolol. Renal hemodynamics may be enhanced, maintained, or adversely influenced depending on the choice of antihypertensive agent.

Acid-base and electrolyte disturbances in anorexia nervosa.

The literature on anorexia nervosa largely ignores the acid-base and electrolyte disturbances that may accompany this condition. In an attempt to assess the magnitude of these disturbances in anorexia nervosa the authors reviewed the laboratory profiles of 7 patients with the disease who were consecutively admitted to a hospital over a period of 8 years. Several acid-base and electrolyte disturbances were observed; the most frequent was chloride-responsive metabolic alkalosis. The authors suggest that all patients with anorexia nervosa receive diagnostic studies for these disturbances, including ECG and urinary electrolytes when necessary, so that abnormalities can be diagnosed and treated appropriately.

Nitroglycerin and nitrate esters.

The expanding applications of nitroglycerin and nitrate esters--in congestive heart failure, in the reduction of infarct size in myocardial infarction and in the long-term prophylaxis of angina--have enhanced the clinical importance of these drugs. This article reviews some of the significant recent investigations of the nitrates and makes specific recommendations regarding clinical use.

Does a renal vasodilator system mediate racial differences in essential hypertension?

Clinical and epidemiologic data support the contention that black people have a higher incidence and severity of essential hypertension than white people, a phenomenon which is likely due to genetic factors. Physiologic profiles in such patients reveal a striking prevalence of low renin, volume-expanded hypertension, with an exaggerated propensity to sodium retention. A deficiency in the natriuretic, vasodilatory renal kallikrein-kinin system may explain these phenomena and may be of practical importance in the selection of therapy.

Myocardial infarction before age 36: risk factor and arteriographic analysis.

One-hundred consecutive patients who were 35 years of age of younger underwent coronary arteriography after clinical myocardial infarction. Ninety-two percent were men. Four distinct subgroups were identified: Ninety-four patients (78 percent) had significant coronary artery disease (greater than 50 percent diameter narrowing of at least one major coronary artery), 20 (17 percent) had normal coronary arteries, 5 (4 percent) had major coronary arterial anomalies and 1 patient had coronary arteritis. Of the patients with obstructive coronary disease, risk factors were smoking in 89 percent, positive family history of coronary artery disease in 48 percent, hypertension in 21 percent and a history of lipid abnormality in 20 percent. Risk factors were distinctly less frequent in the groups without coronary atherosclerosis. In the group with coronary artery disease, the prevalence rate of one, two and three vessel disease was 32, 26 and 42 percent, respectively. Coronary arterial anomalies included anomalous origin of the left coronary artery from the pulmonary artery (three patients) and single right and single left coronary artery (one patient each). It is concluded that myocardial infarction before age 36 is a disease of men who smoke and who often have a family history of premature coronary artery disease. Twenty-two percent of patients will have normal coronary arteries, coronary arterial anomalies or coronary vasculitis. Coronary arteriography should be considered for patients who sustain a myocardial infarction before age 36 for purposes of diagnosis, management and prognosis.

Clinical correlates in hypertensive patients with left ventricular hypertrophy diagnosed with echocardiography.

Seventy-three hypertensive patients were evaluated with M mode and two dimensional echocardiography. Left ventricular hypertrophy was found in 37 patients (51 percent); 29 had concentric hypertrophy and the remaining 8 had disproportionate septal thickening. Factors that did not influence the distribution of patients in the group with left ventricular hypertrophy and normal subjects included (1) duration of hypertension, (2) level of blood pressure, (3) age, (4) body surface area, and (5) race. More of the patients who had a normal left ventricular mass (32 or 89 percent) than of those who had hypertrophy (22 or 59 percent) were receiving two or more antihypertensive drugs. Electrocardiography was very insensitive in identifying left ventricular hypertrophy in these patients. The presence of increased left ventricular mass was associated with a greater incidence of other target organ disease.

Semiautomated method for evaluation of left ventricular regional wall motion in coronary artery disease.

Regional left ventricular wall motion was independently assessed in 436 patients using both subjective visual inspection of ventriculograms and objective computer-determined percent change in the square root of the area between systolic and diastolic outlines. Agreement between subjective and objective techniques was greatest at the ventricular apex and least at the base and partly dependent on the number of abnormal segments present. Objective analysis of regional wall motion provides a permanent quantitative record of wall motion and shows good agreement with meticulous subjective inspection of ventriculograms. As such, it has potential as an adjunct to ventriculography.

Historic and angiographic features of young adults surviving myocardial infarction.

Sixty-eight survivors of myocardial infarction occurring before the age of 36 years were studied using selective coronary cinearteriograms, regardless of symptoms. Three groups of patients were delineated; 56 patients (82 percent) had obstructive coronary arterial disease, nine (13 percent) had normal coronary arteries, and three (4 percent) had congenital coronary arterial anomalies. Because the prognosis in these three groups is different, all young patients with myocardial infarction should undergo coronary arteriographic studies after a suitable period of convalescence. Myocardial infarction in the young differs from that in the elderly by virtue of a more heterogeneous underlying coronary anatomy, an overwhelming preponderance of male patients, and a better reported prognosis.

Occult pulmonary malignancy in syndrome of inappropriate ADH secretion with normal ADH levels.

Although the syndrome of inappropriate ADH secretion (SIADH) has many causes, principally pulmonary, central nervous system or neoplastic disease, and drugs, patients may present with SIADH in whom the etiology is not readily evident. We measured serum ADH levels in such an individual in both the eunatremic and water-loaded states and found levels to be undetectable despite failure to dilute the urine. A small oat cell pulmonary carcinoma was ultimately diagnosed with lung tomograms and cytology. Following a partial response to water restriction, demeclocycline was effective in producing a water diuresis that restored the serum sodium concentration to normal. Patients with clinical SIADH but low serum ADH levels can harbor a malignant or benign process that, notwithstanding the low ADH levels, may still remain responsive to demeclocycline, suggesting either neoplastic production of a biologically-active, immunologically-inactive ADH-like peptide, or increased renal tubular sensitivity to ADH.

Normal single coronary artery and myocardial infarction.

A single left coronary artery was found in an asymptomatic 21-year-old man who initially had electrocardiographic and vectorcardiographic evidence of anterolateral myocardial infarction. The single left coronary artery, which supplied the distribution of both the left and right coronary arteries, was free of disease at catheterization. There has been no previous association of a normal single left coronary artery and anterior myocardial infarction. Patients with the finding of a single coronary artery should be watched closely, as this may represent a potentially fatal condition.

Recurrent spontaneous perforation of the esophagus.

Boerhaave's syndrome is uncommon and its precise etiology is unclear. Information regarding the long-term outcome of patients surviving this injury is lacking. We present the case of a patient who suffered two spontaneous perforations of the esophagus that occurred 30 years apart.

Pulmonary lymphangiomyomatosis causing bilateral pneumothorax during pregnancy.

A 32-year-old woman, 12 weeks pregnant, presented with bilateral spontaneous pneumothorax that did not heal with tube thoracostomy. At right and left thoracotomy, lymphangiomyomatosis of the lung was found and treated by pleurodesis. Lymphangiomyomatosis has been infrequently reported in the surgical literature, even though it may befall the thoracic surgeon to establish the diagnosis and aid in treatment.

Survival of patients with bronchogenic carcinoma modified by BCG immunotherapy.

Fifty-five patients with stage II and III bronchogenic carcinoma were randomized into one group of 21 treated conventionally, and another group of 34 additionally vaccinated with BCG. Vaccinated patients survived, on average, 11 weeks longer than controls. A lag of about six months existed before consistent differences became apparent.