Charles A. Bush

Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in patients with cardiomyopathic heart failure.

SUMMARY Thirteen patients with severe cardiac failure underwent a single crossover study of dopamine and dobutamine in order to compare the systemic and regional hemodynamic effects of the two drugs. The dose-response data demonstrated that dobutamine (2.5-10 μg/kg/min) progressively and predictably increases cardiac output by increasing stroke volume, while simultaneously decreasing systemic and pulmonary vascular resistance and pulmonary capillary wedge pressure. There was no change in heart rate or premature ventricular contractions (PVCs)/min at this dose range. Dopamine (2-8 μg/kg/min) increased the stroke volume and cardiac output at 4, g/kg/min. Dopamine at > 4, Ag/kg/min provided little additional increase in cardiac output and increased the pulmonary wedge pressure and the number of PVCs/min. At > 6 Ag/kg/min, dopamine increased heart rate. During the 24-hour maintenance-dose infusion of each drug (dopamine 3.7-4, dobutamine 7.3-7.7 μg/kg/min), only dobutamine maintained a significant increase of stroke volume, cardiac output, urine flow, urine sodium concentration, creatinine clearance and peripheral blood flow. Renal and hepatic blood flow were not significantly altered by the maintenance dose of either drug. Systemic and regional hemodynamic data suggest that dobutamine has many advantages over dopamine when infused in patients with cardiac failure.

The cardiovascular effects of the continuous infusion of dobutamine in patients with severe cardiac failure.

Twenty-five patients with left ventricular failure and low cardiac output received a 72 hour infusion of dobutamine (10-15 Mg/kg/min) in order to determine the cardiovascular properties of this new inotropic agent. Left ventricular contractile performance improved significantly during the infusion as measured by systolic time intervals and echocardiographic parameters. Mean PEP/LVET decreased from 0.76 ± 0.03 to 0.58 ± 0.03 (P < 0.05). The percent change in internal dimension of the left ventricle from diastole to systole increased from 9.5 ± I to 16.8 ± 1 (P < 0.05) and Vcf increased from 0.47 ± 0.05 to 0.80 ± 0.06 circ/sec (P < 0.05). Mean cardiac output (nine patients) rose from 1.97 ± 0.15 to 3.33 ± 0.50 L/min/m2 while mean pulmonary capillary wedge pressure fell from 28 ± 3 to 18 ± 2 mm Hg during the infusion period (both P < 0.05). These changes in cardiac function occurred without significant changes in heart rate, ventricular irritability, or blood pressure. Urine flow and urine sodium concentration increased during the infusion period. The improvement of cardiac function without the simultaneous development or exacerbation of undesirable effects (tachycardia, premature ventricular contractions, increased pulmonary or systemic resistance, tachyphylaxis, etc.) makes dobutamine a highly desirable inotropic agent.

Aortic distensibility abnormalities in coronary artery disease.

Vasodilatory capacity of nonstenotic arteries in experimental animals with atherosclerosis is decreased. It was postulated that aortic distensibility may be abnormal in patients with coronary artery disease (CAD). Aortic distensibility was determined in 24 normotensive patients with CAD and an angiographically normal aorta and values were compared with those in 18 age-matched normal subjects. Aortic diameters were measured at 3 levels--2, 4 and 6 cm above the aortic valve--by angiographic techniques. The area of the first 6 cm of the aorta above the aortic valve was planimetered and mean aortic diameters were calculated. Distensibility was calculated using the formula: [2 X (changes of the aortic diameter)/(diastolic aortic diameter) X (changes of the aortic pressure)]. CAD patients had similar aortic pressures but markedly lower distensibility than normal subjects: 0.7 +/- 0.2 vs 1.7 +/- 0.3 (p less than 0.02); 1.5 +/- 0.3 vs 4.0 +/- 0.6 (p less than 0.02); and 1.2 +/- 0.2 vs 5.3 +/- 0.6 (p less than 0.001) at 2, 4 and 6 cm above the aortic valve, respectively. Distensibility was also calculated from the mean aortic diameters and was greater in normal subjects than in CAD patients (3.4 +/- 0.4 vs 1.6 +/- 0.1, p less than 0.001). Decreased aortic distensibility in CAD may be related to the common atherosclerotic process or to reduced ascending aorta vasa vasorum flow from coronary arteries.

Occult constrictive pericardial disease. Diagnosis by rapid volume expansion and correction by pericardiectomy.

Significant pericardial disease can exist without overt manifestations. Occult constrictive pericardial disease (OCPD) is identified by normal baseline hemodynamics and normal left ventricular systolic function with a characteristic response to rapid volume infusion. Following the intravenous administration of 1000 ml of normal saline over six to eight minutes, striking elevations of filling pressures are seen; however, diagnosis depends specifically upon a) the development of typical pressure pulse morphology of constriction, b) loss or reversal of respiratory variation of right atrial pressure, and c) precise diastolic equilibration of intracardiac pressures. Nineteen patients with OCPD have been identified in a five year period. Unexplained fatigue, dyspnea and chest pain was the uniform pattern of presentation. Eleven have undergone pericardiectomy resulting in a dramatic symptomatic improvement in all. Each demonstrated gross and/or microscopic evidence of pericardial disease. Recatheterization with volume infusion in five patients following pericardiectomy has revealed return to normal or near normal hemodynamics. This study describes the method for diagnosis of OCPD and recommends pericardiectomy for the management of disabling symptoms.

Assessment of left ventricular pressure-volume relations using gated radionuclide angiography, echocardiography, and micromanometer pressure recordings. A new method for serial measurements of systolic and diastolic function in man.

This study was designed to validate the use of combined invasive and noninvasive methods in assessing serial pressure-volume relations in man. Ten patients undergoing cardiac catheterization were studied with simultaneous intracardiac micromanometer pressure recordings, gated radionuclide angiography and echocardiography. Systolic and diastolic function were measured at rest, during right atrial pacing rates of 100 and 120 beats/min and after nitroglycerin administration. Right atrial pacing studies (rate of 100 beats/min) were performed in duplicate to determine the reproducibility of the method. At the conclusion of each study, the model was validated with contrast angiography. Good reproducibility was evident when measuring the maximum and average filling and ejection rates, time to peak filling rate, ejection fraction, the modulus of chamber stiffness, the time course of left ventricular relaxation, global average stress and ventricular work indexes using the model described above. These data were not significantly different (p > 0.05) from comparable data obtained from contrast angiography. Right atrial pacing and nitroglycerin administration resulted in predictable alterations in the pressure-volume loop and in the systolic and diastolic measurements. The maximum and average filling rates, ejection rates and time to peak filling rate appeared to be heart rate-dependent variables. By combining available invasive and noninvasive methods, accurate pressure-volume relationships can be determined. Because the method we tested provides accurate volumetric and timing measurements for cardiac events and does not alter hemodynamics, it may be useful for obtaining serial assessments of the pressure-volume relationship in man.

Hemodynamic correlates for timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve☆

This study was designed to more clearly define the relation between various invasive hemodynamic measurements and left ventricular (LV) timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve. Twenty-eight patients were studied with simultaneous intracardiac micromanometer pressure and dP/dt recordings, gated radionuclide angiography and M-mode echocardiography. These techniques permitted multiple variables of systolic and diastolic function to be measured at a constant atrial paced rate of 100 beats/min. There was a strong correlation between peak ejection rate and ejection fraction (r = -0.97) and between peak ejection rate and maximum positive dP/dt (r = -0.85). There also was a strong correlation between peak filling rate and maximum negative dP/dt (r = -0.85). A weaker correlation existed between the time constant of LV relaxation and the peak filling rate (r = -0.49) and between the LV end-diastolic pressure and the peak filling rate (r = -0.62). There was no correlation between the modulus of chamber stiffness and filling rates, and no association was observed between the time to peak filling rate and the hemodynamic variables. Thus, under the conditions studied, the measured peak ejection and filling rate, determined from the radionuclide angiographic volume curve, correlated well with accepted invasive hemodynamic measurements.

Coronary collateral vessels: Spectrum of physiologic capabilities with respect to providing rest and stress myocardial perfusion, maintenance of left ventricular function and protection against infarction

Abstract The physiologic significance of coronary collateral vessels was evaluated in 91 patients with stable coronary artery disease. Four physiologic variables were assessed in the distribution areas of 101 totally occluded coronary arteries associated with angiographically defined collateral vessels. These variables included myocardial perfusion at rest and during stress, left ventricular wall motion and the presence or absence of myocardial infarction. These 101 collateralized areas of myocardium were classified into two major groups on the basis of normal (43 areas) or abnormal (58 areas) myocardial perfusion at rest. Among the 43 areas with normal perfusion at rest, three or more variables were normal in 37 instances (86 percent) and all variables were normal in 17. Of 58 areas with abnormal perfusion at rest, three or more variables were abnormal in 47 (81 percent), and all four variables were abnormal in 32. Although the results were generally concordant when all variables were assessed as a group, significant discrepancies existed if each variable was compared individually with resting perfusion. Of the 43 areas with normal resting perfusion 14 (33 percent) had stress defects, 15 (35 percent) had wall motion abnormalities and 5 (12 percent) showed electrocardiographic evidence of myocardial infarction. Of the 58 areas with abnormal resting perfusion 5 (9 percent) had normal stress perfusion, 16 (28 percent) had normal wall motion and 22 (38 percent) lacked electrocardiographic evidence of infarction. The presence or absence of significant coronary artery disease distal to the origin of a collateral vessel, the extent of coronary artery disease in all coronary vessels and the angiographic appearance of collateral vessels were not helpful in defining the significance of a collateral vessel. These results indicate that the functional significance of collateral vessels varies considerably. Collateral vessels in many patients may be highly effective in maintaining myocardial perfusion and left ventricular function and preventing infarction; in others, collateralization may be of no significance. The use of multiple variables as a group rather than individually provides meaningful information regarding the physiologic significance of a collateral vessel and complements the coronary angiogram, which is not uniformly helpful in making this assessment.

Evidence for progression from mild to severe mitral regurgitation in mitral valve prolapse.

Little information is available concerning the progression of mild to severe mitral regurgitation (MR) in patients with mitral valve prolapse (MVP). This study reports 86 patients, average age 60 years, who presented with cardiac symptoms, precordial systolic murmur, severe MR and a high incidence of MVP on echocardiography (57 of 75 [75%] ) and left ventriculography (61 of 84 [73%] ). Seventy-five surgically excised mitral valves appeared grossly enlarged and floppy. Histologic studies showed extensive myxomatous changes throughout the leaflets and chordae. Eighty patients had had precordial murmurs first described at average age 34 years, but the average age at which symptoms of cardiac dysfunction appeared was 59. However, once symptoms developed, mitral valve surgery was required within 1 year in 67 of 76 patients who had undergone surgery. Atrial fibrillation, present in 48 of 86 patients (56%), or ruptured chordae tendineae, present in 39 of 76 patients (51%), may have contributed to this rapid progression and deterioration. Additionally, 13 patients had a remote history of documented infective endocarditis. Twenty-eight patients had at least 1 type of serial clinical evaluation that indicated progressive MR in all 28 patients on the basis of changing auscultatory findings (24 of 26), progressive radiographic cardiomegaly (24 of 25), echocardiographic left atrial enlargement (4.3 to 5 cm in 11 patients) and angiographically worsening MR (14 of 15). Twenty-four of these patients had evidence of MVP on at least 1 of their initial studies. Thus, mild MR due to MVP and myxomatous mitral valves is a progressive disease in some patients with MVP.

Improvement of myocardial perfusion and left ventricular function after coronary artery bypass grafting in patients with unstable angina.

Changes in myocardial perfusion and left ventricular function were evaluated pre- and postoperatively (3-6 months) in 14 patients with unstable angina who underwent coronary artery bypass surgery. Perfusion was studied with intracoronary and intragraft injections of radiolabeled macroaggregated albumin particles. Of 20 abnormal perfusion areas identified preoperatively, 13 demonstrated improved perfusion postoperatively. Segmental analysis of the left ventriculogram demonstrated improved wall motion in 29 abnormally contracting segments; 18 normalized. Areas which showed improvement of left ventricular perfusion were invariably associated with improvement of left ventricular wall motion. Five patients showed improvement in perfusion and contraction in areas of apparent old myocardial infarction. Thirteen of the 14 patients had significantly less angina whether or not there was evidence of improved perfusion. However, only those patients who demonstrated improved perfusion had a significant improvement in their treadmill exercise tolerance postoperatively. Thus, patients with unstable angina have perfusion defects which may be reversed as a result of saphenous vein graft surgery. Reversal of these perfusion abnormalities results in improved left ventricular performance and better exercise tolerance postoperatively.

Hemorrhagic ocular complications associated with the use of systemic thrombolytic agents

OBJECTIVE This study aimed to report three patients with hemorrhagic ocular and orbital complications associated with the use of systemic thrombolytic agents. DESIGN The study design was a retrospective small case series. PARTICIPANTS Three eyes of three patients were studied. INTERVENTION Surgical procedures to reduce intraocular pressure or relieve optic nerve compression were performed. MAIN OUTCOME MEASURES Visual acuity and intraocular pressure were measured. RESULTS Three patients received an intravenous thrombolytic agent on diagnosis of an acute myocardial infarction. One patient had a spontaneous suprachoroidal hemorrhage develop with secondary acute angle closure glaucoma shortly after receiving tissue plasminogen activator. Another patient had an orbital hemorrhage develop on receiving tissue plasminogen activator 4 days after an uncomplicated cataract extraction. The third patient experienced an orbital hemorrhage while receiving streptokinase 1 day after undergoing an external levator resection. Two patients suffered significant visual loss due to glaucoma or compressive optic neuropathy. CONCLUSIONS The onset of eye pain or visual loss after the administration of a systemic thrombolytic agent should alert the physician to the possibility of an ocular or adnexal hemorrhage. Prompt diagnosis and treatment can improve the likelihood of a favorable visual outcome.