Biomedical subjects
Publications and source records attributed to K G Morris.
This report describes a digital subtraction angiographic technique used to simultaneously display the proximal and distal segments of three totally occluded coronary arteries in two patients undergoing percutaneous transluminal coronary angioplasty (PTCA). The advantage of this technique over routine cineangiography for PTCA of total occlusions is illustrated.
To determine the physiologic mechanisms of the decline in aerobic work performance with age, a cross-sectional study was performed. Twenty-four sedentary male volunteers, aged 20 to 50 years, underwent right-sided cardiac catheterization, arterial cannulation, radionuclide angiography and expired gas analysis for detailed evaluation of central and peripheral cardiovascular function during submaximal and maximal exercise. Habitual physical activity level varied but was well matched across the age range. Over the 3-decade age range studied, there was no detectable change in cardiovascular function at rest. When peak exercise variables were examined, an age-related 25% decrease in O2 consumption was noted (r = -0.43, p = 0.04); this was associated with a 25% decrease in peak cardiac index (r = -0.54, p = 0.01) and a 20% decrease in peak heart rate (r = -0.63, p = 0.002). In addition, there was an age-related increase in calculated systemic and pulmonary vascular resistances and an increase in left ventricular ejection time. No age relation was seen for exercise stroke volume index, end-diastolic volume index, end-systolic volume index, pulmonary artery wedge pressure, ejection fraction or arteriovenous O2 difference. These results indicate that the age-related decline in aerobic work performance among men aged 20 to 50 years results primarily from a reduced exercise heart rate in older subjects rather than from a reduction in stroke volume or peripheral O2 utilization.
The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo-controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
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The mechanism of hypoxic pulmonary vasoconstriction is still unclear. Since leukotrienes are pulmonary vasoconstrictors and lung cells are able to produce leukotrienes, it has been proposed that leukotrienes are mediators of hypoxic pulmonary vasoconstriction and then inhibition of their synthesis should block hypoxic pressure responses. In order to test this hypothesis we investigated whether diethylcarbamazine (DEC), a known leukotriene synthesis blocker, blocks hypoxic pulmonary vasoconstriction in isolated rat lungs. DEC blocked ongoing and subsequent hypoxic pressure responses in a relatively specific and dose-dependent fashion. We therefore extended our observations to awake rats and found that DEC reversibly inhibited acute hypoxic pulmonary vasoconstriction. Furthermore, pulmonary hypertension and right ventricular hypertrophy in rats exposed to chronic hypobaric hypoxia could be prevented by DEC treatment. From these data we conclude that DEC inhibits both acute and chronic hypoxic pulmonary vasoconstriction. Thus, leukotrienes could be important mediators of hypoxic pulmonary vasoconstriction.
This prospective study evaluated the ability of serial biplane rest and exercise radionuclide angiography to predict the status of individual coronary bypass grafts in 20 patients 2 to 6 months after surgery. The preoperative coronary angiogram was used to assign vessels to 10 regions of distribution on the radionuclide angiogram. Predictions of graft adequacy for individual vessels were based on a detailed assessment of rest and exercise wall motion in their regions of supply. Of 59 grafts, 38 were judged adequate (patent with less than 75% stenosis) and 21 inadequate by postoperative catheterization. Radionuclide prediction of graft status was possible for 32 of the 59 grafts, including 19 of 24 left anterior descending, 7 of 19 circumflex and 6 of 16 right coronary artery grafts. The status of the remaining 27 grafts could not be assessed because of normal wall motion in their region of supply both pre- and postoperatively (22 vessels) or because a region of supply was not represented on the biplane radionuclide angiogram (5 vessels). Of the 32 predictions made, 25 (78%) were correct, including 13 (93%) of 14 predictions of graft adequacy and 12 (67%) of 18 predictions of graft inadequacy. The single incorrect prediction of graft adequacy resulted from improved exercise wall motion in a region supplied by a graft judged as having a 75% anastomotic stenosis. Most incorrect predictions of graft inadequacy were due to new septal or other rest wall motion abnormalities postoperatively. The comparison of pre- and postoperative studies was essential to maintain the predictive ability of the test. Thus, a detailed analysis of regional wall motion by rest and exercise radionuclide angiography can be used to predict the status of individual coronary artery bypass grafts. Reliable predictions can be made for most successful anterior descending grafts, and may permit cardiac catheterization to be deferred in certain cases. However, the method is limited by the need to perform preoperative exercise studies, by the low number of right and circumflex coronary artery grafts that can be evaluated and by the poor specificity of predictions of graft failure.
To characterize the hemodynamic factors that regulate stroke volume during upright exercise in normal man, 24 asymptomatic male volunteers were evaluated by simultaneous right heart catheterization, radionuclide angiography, and expired gas analysis during staged upright bicycle exercise to exhaustion. From rest to peak exercise, oxygen consumption increased from 0.33 to 2.55 liters/min (7.7-fold), cardiac index increased from 3.0 to 9.7 liters/min per m2 (3.2-fold), and arteriovenous oxygen difference increased from 5.8 to 14.1 vol% (2.5-fold). The increase in cardiac index resulted from an increase in heart rate from 73 to 167 beats/min (2.5-fold), and an increase in left ventricular stroke volume index from 41 to 58 ml/m2 (1.4-fold). During low levels of exercise, there was a linear increase in cardiac index due to an increase in both heart rate and stroke volume index; stroke volume index increased as a result of an increase in left ventricular filling pressure and end-diastolic volume index and, to a much smaller extent, a decrease in end-systolic volume index. During high levels of exercise, further increases in cardiac index resulted entirely from an increase in heart rate, since stroke volume index increased no further. Left ventricular end-diastolic volume index decreased despite a linear increase in pulmonary artery wedge pressure; stroke volume index was maintained by a further decrease in end-systolic volume index. The degree to which stroke volume index increased during exercise in individuals correlated with the change in end-diastolic volume index (r = 0.66) but not with the change in end-systolic volume index (r = 0.07). Thus, the mechanism by which left ventricular stroke volume increases during upright exercise in man is dependent upon the changing relationship between heart rate, left ventricular filling, and left ventricular contractility. At low levels of exertion, an increase in left ventricular filling pressure and end-diastolic volume are important determinants of the stroke volume response through the Starling mechanism. At high levels of exertion, the exercise tachycardia is accompanied by a decrease in end-diastolic volume despite a progressive increase in filling pressure, so that stroke volume must be maintained by a decrease in end-systolic volume.
Although platelet-activating factor (PAF) has generally been found to be a pulmonary pressor substance, its vasoactivity has not been measured at low doses in a preconstricted pulmonary vascular bed. Thus, we examined the effects of low concentrations of PAF on systemic and pulmonary hemodynamics during normoxia and acute hypoxia in conscious, catheterized rats (weighing 250 to 350 g), on hypoxic vasoconstriction in isolated rat lungs, and on norepinephrine-induced constriction in isolated, intact, and endothelium-denuded rat pulmonary arteries. In normoxic rats, injections of 0.001, 0.01, 0.1, and 1.0 microgram PAF/rat given intravenously caused progressively greater, transient systemic hypotension and tachycardia. The 2 higher doses also decreased cardiac output and pulmonary arterial pressure (Ppa). In 5 rats breathing 8% O2, Ppa fell from 36 +/- 2 to 30 +/- 2 torr within 1 min of injection of 0.01 microgram PAF and did not change (39 +/- 2 versus 40 +/- 2 torr) 1 min after 0.25% albumin (vehicle). Total pulmonary resistance was 0.18 +/- 0.04 torr/ml/min in normoxic rats and 0.19 +/- 0.04 and 0.28 +/- 0.06 torr/ml/min, respectively, in hypoxic rats receiving 0.01 microgram PAF or vehicle. The PAF (10(-10) to 10(-8) g/ml) also reversed hypoxic vasoconstriction in isolated lungs perfused at constant flow. Lungs perfused with salt solution but not those with blood became rapidly densensitized to PAF-induced vasodilation. After constriction with 10(-6) M norepinephrine, both acetylcholine (10(-7) to 10(-6) M) and PAF (10(-10) to 10(-9) g/ml) dilated intact but not endothelium-denuded pulmonary artery rings.(ABSTRACT TRUNCATED AT 250 WORDS)
The value of rest and exercise radionuclide angiography (RNA) for predicting specific events including death, recurrent acute myocardial infarction (AMI), coronary care unit readmission for unstable chest pain, and medically refractory angina after AMI was studied in 106 consecutive survivors of AMI. Analysis of the RNA variables using the Cox proportional hazards regression model yielded significant associations of the time to death with ejection fraction at rest and during exercise (X2 = 11.1 and 14.0, respectively). Both variables added significant prognostic information to the clinical assessment (X2 = 4.3 and 5.7, respectively). The change in ejection fraction from rest to exercise predicted the time to coronary artery bypass grafting for medically refractory angina before (X2 = 21.0) and after (X2 = 13.2) adjustment for the clinical descriptors, but did not predict death or other non-fatal events. Significant correlations were found between RNA variables and a variety of clinical descriptors previously reported to have prognostic significance. Clinical and RNA variables that are measures of left ventricular function were predictive of subsequent mortality, whereas those that reflect residual potentially ischemic myocardium were predictive of subsequent nonfatal ischemic events. Rest and exercise RNA after AMI provides significant prognostic information regarding specific events during follow-up independent of that provided by clinical assessment.
The change in left ventricular radionuclide ejection fraction after acute occlusion of the left anterior descending (LAD) or circumflex (LC) coronary artery was compared with the ultimate histologic extent of myocardial infarction in conscious dogs. The acute change in ejection fraction correlated with size of infarction in 14 dogs with occlusions of the LAD coronary artery (r = .89, y = 1.12x + 14.2) and in 27 dogs with occlusions of the LC coronary artery (r = .71, y = 0.73x + 7.9); the slope of the regression equation was greater (p less than .05) for those with LAD than for those with LC occlusions. Multivariate analysis revealed no independent contribution of left ventricular weight, the subendocardial extent of infarction, or change in heart rate to the acute change in ejection fraction. These data indicate that the decrease in ejection fraction after coronary occlusion is determined primarily by the size of the ischemic area, which also determines size of infarction. In dogs instrumented over a long term, infarcts in the LAD myocardial distribution result in greater decreases in ejection fraction than infarcts of comparable size in the LC distribution.
Leukotriene inhibitors preferentially inhibit the acute pressor response to hypoxia in isolated rat lungs. If leukotrienes are important in hypoxic pulmonary vasoconstriction, then inhibition of their synthesis could prevent the development of chronic hypoxic pulmonary hypertension. We found that diethylcarbamazine (DEC), a leukotriene synthesis blocker, reversibly inhibited acute hypoxic pulmonary vasoconstriction in the awake rat. Rats exposed to chronic hypobaric hypoxia showed pulmonary hypertension and the production of a slow-reacting substance compared with low altitude control rats. The higher of 2 doses of DEC blocked the pulmonary hypertension and the production of slow-reacting substance in all of the hypoxic rats treated. The lower dose of DEC attenuated the pulmonary hypertension in only some of the rats. Changes in weight gain, hematocrit, or generation of prostacyclin did not explain the prevention of the pulmonary hypertension by DEC. We conclude that diethylcarbamazine inhibits acute and chronic pulmonary hypertension in the intact rat.
A simple method for the assessment of regional left ventricular (LV) function using gated radionuclide angiography is described. The method divides the LV region of interest in the left anterior oblique view into quadrants using a count-weighted center point and a transparent overlay. The regional ejection fraction (EF) was determined at rest and during upright bicycle exercise for each of 3 quadrants identified as posterior, septal and apical. The study group consisted of 50 patients with chest pain. Nine of these patients had normal coronary arteries and 41 had significant coronary artery disease (CAD). Regional EF measurements were highly reproducible at rest and exercise in all regions. Regional EF values at rest were compared with the subjective assessment of wall motion on the contrast ventriculogram and were significantly lower in regions with abnormal wall motion. Regional EF increased with exercise in all patients with normal coronary arteries. In patients with CAD and normal regional wall motion at rest, the regional exercise response was significantly more sensitive (p = 0.004) than global exercise response and marginally more sensitive (p = 0.06) than the subjective assessment of exercise wall motion on visual radionuclide images in the diagnosis of CAD. These results suggest that the measurement of regional LV function may be useful in the noninvasive diagnosis of CAD.
Multigated equilibrium radionuclide angiography was used to quantitate global and regional ejection fraction (EF) in 26 awake dogs 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD) or left circumflex (LC) coronary artery. Changes in global and regional EF were correlated with simultaneous measurements of the extent of acute left ventricular (LV) ischemia measured by radioisotope-labeled microspheres. The extent of ischemia, defined as the percentage of LV mass with greater than 25% reduction in blood flow from normal regional flow, was linearly related to the percent change in global EF after LAD (r = 0.84) and LC (r = 0.77) occlusions. The extent of ischemia also correlated with regional EF (r = 0.47 to 0.88 for LAD and r = 0.41 to 0.69 for LC occlusions). In 24 of 25 LAD occlusions and in all 20 LC occlusions that produced a measurable ischemic zone, the maximal percent change in regional EF exceeded the percent change in global EF. Two LAD occlusions and 2 LC occlusions reduced regional EF but not global EF. Thus, global and regional EF decreased in direct proportion to the extent of acute myocardial ischemia; regional ischemia produced greater changes in regional than in global EF.
We studied 109 consecutive patients with variant angina who underwent cardiac catheterization over an 11 year period. All patients were followed for at least 6 months or until death, and 46 patients (22 treated medically and 24 treated surgically) were followed for 5 years or more. Of the 62 patients initially treated medically, 14 had nonfatal myocardial infarctions (12 within 1 month of catheterization) and 12 died (six within 6 months). Survival probabilities at 1, 3, and 5 years were 0.88, 0.84, and 0.77, respectively. Of the 48 surgically treated patients (including four patients initially treated medically and one initially treated with coronary angioplasty), four had nonfatal infarctions (three in the perioperative period) and three died (all in the perioperative period). The survival probability in these patients at 1 year was 0.94 and remained unchanged at 3 and 5 years. Only one nonfatal infarction and no deaths have occurred in the group of surgically treated patients subsequent to hospital discharge. Three additional patients were treated with coronary angioplasty. The single most important prognostic factor in medically treated patients was the presence or absence of fixed obstructive coronary artery disease. Infarction-free survival probabilities at 1 and 3 years in the 23 patients without significant coronary artery disease were 1.0 and 0.89, compared with 0.51 and 0.46 in the 39 patients with significant coronary disease. Analysis by the Cox model showed that variant angina patients had a higher probability of death and nonfatal infarction than did those with nonvariant angina coronary disease if other important prognostic variables were held constant.(ABSTRACT TRUNCATED AT 250 WORDS)
In previous studies from this laboratory, we found that approximately 30% of women with chest pain and normal coronary arteries demonstrated either a decrease in or a failure to increase radionuclide ejection fraction during exercise. To examine the hypothesis that this apparent abnormality in left ventricular function represents a physiologic difference between men and women, we prospectively studied central and peripheral cardiovascular responses to exercise in 31 age-matched healthy volunteers (16 women and 15 men). A combination of quantitative radionuclide angiography and expired-gas analysis was used to measure ejection fraction and relative changes in end-diastolic counts, stroke counts, count output, and arteriovenous oxygen difference during symptom-limited upright bicycle exercise. Normal male and female volunteers demonstrated comparable baseline left ventricular function and similar aerobic capacity, as determined by weight-adjusted peak oxygen consumption (22.1 +/- 5.1 and 22.6 +/- 4.3 ml/kg/min, respectively). However, their cardiac responses to exercise were significantly different. Ejection fraction increased from 0.62 +/- 0.09 at rest to 0.77 +/- 0.07 during exercise in men (p less than .001), but was unchanged from 0.63 +/- 0.09 at rest to 0.64 +/- 0.10 during exercise in women. The ejection fraction increased by 5 points or more in 14 of 15 men, but in only seven of the 16 women. End-diastolic counts increased by 30% in women (p less than .001), but was unchanged in men. Because decreases in ejection fraction were matched by increases in end-diastolic counts, relative increases in stroke counts and count output were the same for men and women. These data demonstrate a basic difference between men and women with respect to the mechanism by which they achieve a normal response of stroke volume to exercise; these differences must be taken into account when measurements of cardiac function during exercise stress are used for diagnostic purposes.
There exists no agreement as to the best vasodilator drug for treatment of hypoxic pulmonary hypertension. We wondered which of 3 commonly used vasodilators - verapamil, nifedipine, or hydralazine - would be the most effective in reducing and reversing the development of hypoxic pulmonary hypertension in the conscious rat. Hemodynamic studies showed that all 3 drugs inhibited the pressor response to acute hypoxia. Given for 1 month to conscious rats during exposure to intermittent hypoxia, verapamil and nifedipine reduced pulmonary hypertension when compared with hypoxic control animals, as indicated by right ventricular hypertrophy, total pulmonary resistance, and medial thickening. Hydralazine caused similar, but smaller, changes. Nifedipine, when used to reverse established hypoxic pulmonary hypertension, reduced right ventricular hypertrophy and medial thickening. Cardiac and systemic effects were negligible. These results demonstrate that the calcium channel blockers reduce the development of hypoxic pulmonary hypertension and that nifedipine partially reverses established hypertension.
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The relation between bicycle exercise performance and determinants of central and peripheral cardiovascular function was assessed in 17 patients with class II to III heart failure and in 9 normal subjects. Proportional changes in oxygen consumption (VO2) from rest (R) to maximal exercise (Ex), or Mets, were used as an objective measure of the exercise capacity or functional reserve of the cardiovascular system. Left ventricular ejection fraction (EF) and proportional changes in end-diastolic volume, stroke volume, and cardiac output were determined from appropriate count data by equilibrium radionuclide angiography. Proportional changes in arteriovenous oxygen difference (A-VO2) were derived from the equation Ex/R A-VO2 = Ex/R VO2 divided by Ex/R CO, where CO = count output. Each subject exercised to an anaerobic endpoint. Maximal VO2 was significantly lower in patients than in normal subjects. Because Ex/R A-VO2 was comparable in normal subjects and patients, the lower exercise performance in patients resulted from a reduced count output response. The reduced CO response in patients resulted from failure of the ejection fraction to increase or from an attenuated heart rate response, or both. Exercise performance was variable in both groups. Multivariable analysis in the patient group identified changes in heart rate, count output, and A-VO2 with exercise as important predictors of Mets, but found no relation between Mets and changes in ejection fraction or stroke counts during exercise. Similarly, multiple regression analyses between Mets and determinants of cardiovascular function demonstrated significant correlations with Ex/R heart rate, Ex/R count output, and Ex/R A-VO2 in both groups. In patients, EF at rest ranged from 0.09 to 0.36, but it did not correlate with Mets, nor did changes in ejection fraction, stroke counts, or end-diastolic counts during exercise. The variable exercise performance among patients with severe left ventricular dysfunction was determined predominantly by a variable heart rate and A-VO2 response and not by rest or exercise indexes of left ventricular function.