Right main coronary artery disease: antemortem diagnosis and treatment.
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Coronary Disease↗
Biomedical subjects
M A Fifer
Publications and source records attributed to M A Fifer.
Altered left ventricular diastolic properties during pacing-induced angina in patients with aortic stenosis.
An increase in left ventricular diastolic pressure has been repeatedly observed during angina in patients with coronary artery stenoses and regional demand ischemia, but the role of relaxation abnormalities versus left ventricular segmental dyssynchrony is controversial. In contrast, patients with angina due to aortic stenosis are likely to have diffuse rather than segmental ischemia and thus may provide an alternative model for examining the diastolic physiology of angina in man. Accordingly, we examined the hemodynamic manifestations of angina in eight patients with aortic stenosis without significant coronary artery disease. Angina was induced by pacing tachycardia, and hemodynamic and echocardiographic variables were measured in the control period and during angina in the beats immediately after cessation of pacing. Heart rate (control vs angina, 69 +/- 12 vs 70 +/- 11 beats/min, p = NS) and left ventricular peak systolic pressure (207 +/- 39 vs 222 +/- 22 mm Hg, p = NS) were similar in the control and postpacing angina periods. Left ventricular end-diastolic pressure, on the other hand, was significantly higher during postpacing angina (15 +/- 7 vs 28 +/- 8 mm Hg, p less than .01). The time constant of left ventricular pressure decline during isovolumetric relaxation (TL), calculated as the slope of a linear fit of the natural log of pressure vs time, increased from 44 +/- 5 to 51 +/- 7 msec (p less than .05); the time constant TD, derived from the slope of a linear fit of dP/dt vs pressure, also increased slightly, although the change was not statistically significant (69 +/- 5 vs 75 +/- 5 msec, p = .06).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Milrinone and dobutamine in severe heart failure: differing hemodynamic effects and individual patient responsiveness.
Milrinone and dobutamine were compared in 15 patients with New York Heart Association functional class III and IV congestive heart failure. Dobutamine and milrinone were administered intravenously according a graded titration schedule up to maximum doses (14 micrograms/kg/min and 75 micrograms/kg, respectively) or until increased ventricular ectopy or a reduction in left ventricular end-diastolic pressure to 10 mm Hg or less occurred. Although both agents markedly increased cardiac index, milrinone caused a significantly greater reduction in left and right heart filling pressures and mean arterial pressure than did dobutamine, and for any given increase in dP/dt, milrinone caused a greater reduction in systemic vascular resistance than did dobutamine. Thus, the hemodynamic effects of milrinone are best represented by a combination of the actions of dobutamine, a positive inotropic agent, and a vasodilator such as nitroprusside, which causes both arterial and venous dilation. The positive inotropic responses of individual patients to dobutamine (5 micrograms/kg/min) and milrinone (25 micrograms/kg) were compared. The increases in dP/dt with both agents were variable, and correlated poorly (r = .50; p = .059). Patients were divided into two groups: Group I consisted of eight patients in whom the ratio of the increase in dP/dt with dobutamine vs milrinone was greater than 1.0 (good dobutamine responders); group II consisted of seven patients in whom this ratio was less than 1.0 (poor dobutamine responders).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
The creatine kinase system in normal and diseased human myocardium.
We measured creatine kinase activity, isozyme composition, and total creatine content in biopsy samples of left ventricular myocardium from 34 adults in four groups: subjects with normal left ventricles, patients with left ventricular hypertrophy due to aortic stenosis, patients with coronary artery disease without left ventricular hypertrophy, and patients with coronary artery disease and left ventricular hypertrophy due to aortic stenosis. As compared with specimens of normal left ventricles, those from all patients with left ventricular hypertrophy had lower creatine kinase activity, higher MB creatine kinase isozyme content and activity, and lower creatine content. Specimens from the patients without left ventricular hypertrophy had normal creatine kinase activity, increased MB creatine kinase isozyme content and activity, and decreased total creatine content. The normal ventricles showed almost no MB isozyme content or activity. These data suggest that changes in the creatine kinase system occur in both pressure-overload hypertrophy and coronary artery disease. Patients with myocardial infarction who have mild or no preexisting fixed coronary artery disease or pressure-overload hypertrophy would not be expected to have elevation of serum MB creatine kinase.
Adult↗
Calcium channel blockers in congestive heart failure: theoretic considerations and clinical experience.
Although it has been suggested that calcium channel blocking agents may be utilized as vasodilators in patients with congestive heart failure, these agents also have the potential to cause a deterioration in cardiac function because of their negative inotropic actions. There is considerable variation among the available agents with regard to their relative effects on the vasculature, myocardial inotropy, and myocardial chronotropy. Thus, at clinically relevant dosages, nifedipine is a potent systemic and coronary vasodilator, but it has little or no direct effect on inotropy and chronotropy. In contrast, verapamil exerts significant negative inotropic and chronotropic effects at vasodilatory dosages, whereas diltiazem is a potent vasodilator with a negative chronotropic action at dosages that do not affect inotropy. In patients with heart failure, the largest experience so far has been with nifedipine. Data derived from over 100 patients with moderate to severe congestive heart failure indicate a generally beneficial net hemodynamic response to nifedipine, with substantial improvements in cardiac index (+24 percent) and left ventricular filling pressure (-15 percent). The major effect seems to be on arteriolar resistance vessels, resulting in a reduction in afterload, with relatively little effect on venous pressures. Limited data suggest that the initial effect is sustained during long-term therapy. The clinical experience with verapamil and diltiazem in patients with heart failure is at present limited. In patients with normal or mildly impaired left ventricular function, verapamil's vasodilator and negative inotropic effects are counterbalanced. With severe left ventricular dysfunction, however, treatment with verapamil can result in abrupt decompensation and development of overt pulmonary edema and hypotension. Diltiazem's relative lack of negative inotropic effects may allow it to be used safely in patients with congestive heart failure, particularly when control of supraventricular tachyarrhythmia is required.
Calcium↗
Early diastolic left ventricular function in children and adults with aortic stenosis.
Pressure overload hypertrophy of the left ventricle is associated with abnormal left ventricular early diastolic filling. The roles of the extent of cardiac hypertrophy, depressed left ventricular systolic function and aging in the pathogenesis of left ventricular diastolic dysfunction have not, however, been fully defined. To determine the relative importance of these factors in the pathogenesis of diastolic dysfunction in pressure overload hypertrophy, 16 children and 25 adults with aortic stenosis were compared with 48 normal children and adults, using rates of left ventricular early diastolic filling and wall thinning derived from M-mode echocardiography. Left ventricular early diastolic filling and wall thinning rates were significantly depressed in both children and adults with aortic stenosis as compared with values in normal subjects. Filling and thinning rates correlated negatively with age, left ventricular peak systolic pressure and wall thickness in all subjects. Furthermore, the effect of age on diastolic function appeared to be mediated by age-related increases in systolic pressure and wall thickness. In adults with aortic stenosis, early diastolic filling and wall thinning rates were depressed to a similar extent in subjects with normal and abnormal systolic function; thus, diastolic dysfunction does not appear to be a manifestation of abnormal systolic loading and ejection performance. These results suggest that extent of hypertrophy itself plays a dominant role in the mechanism of impaired left ventricular early diastolic filling in pressure overload due to aortic stenosis.
Adolescent↗
Inotropic, vascular and neuroendocrine effects of nifedipine in heart failure: comparison with nitroprusside.
To evaluate the short-term hemodynamic and neuroendocrine effects of nifedipine in heart failure, it was compared with nitroprusside, a balanced vasodilator without known inotropic effect, in equihypotensive doses during right and left heart catheterization in nine patients with heart failure. Mean arterial pressure decreased from 89 +/- 12 to 76 +/- 14 mm Hg with nitroprusside, and from 90 +/- 12 to 75 +/- 13 mm Hg with sublingual nifedipine. Right atrial, pulmonary artery, pulmonary capillary wedge and left ventricular end-diastolic pressures decreased significantly with nitroprusside, but not with nifedipine. Cardiac index and stroke volume index increased to a similar extent with both drugs; in contrast, stroke work index increased significantly with nitroprusside, but not with nifedipine. Peak rate of left ventricular pressure development (dP/dt) (measured with a micromanometer-tipped catheter in seven patients) was unchanged with nitroprusside, but decreased significantly with nifedipine (747 +/- 292 to 639 +/- 238 mm Hg/s; p less than 0.002). There was no change in heart rate with either medication. Plasma norepinephrine and epinephrine concentrations were not altered significantly by either drug. Plasma renin activity was not changed by nitroprusside infusion, but was increased after the administration of nifedipine. Thus, in contrast to the balanced vasodilator action of nitroprusside, the effect of nifedipine is predominantly on the arterial circulation. In these patients with heart failure, reflex sympathetic stimulation did not occur in response to a decrease in systemic arterial pressure by either vasodilator. A negative inotropic effect occurred after the administration of nifedipine, but not nitroprusside.
Adult↗
End-systolic pressure-volume and stress-length relations in the assessment of ventricular function in man.
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Animals↗
Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside.
Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared with nitroprusside for a matched reduction in mean aortic pressure or systemic vascular resistance, milrinone caused a significantly greater increase in stroke work index at the same or lower left ventricular end-diastolic pressure. Milrinone caused a concentration-related increase in dP/dt (32% increase at maximum milrinone dose), whereas nitroprusside had no effect. These data in patients with severe heart failure indicate that in addition to a vasodilating effect, milrinone exerts a concentration-related positive inotropic action that contributes significantly to the drug's overall hemodynamic effects. The positive inotropic action occurs at drug levels that do not exert significant chronotropic or vasodilator effects.
Adult↗
Improvement in indexes of diastolic performance in patients with congestive heart failure treated with milrinone.
To elucidate the mechanisms by which the new bipyridine inotropic agent milrinone improves cardiac function, we examined multiple indexes of left ventricular diastolic function before and after administration of milrinone to patients with advanced (NYHA class III or IV) congestive heart failure. In 13 patients left ventricular pressure measurements were made with a micromanometer to permit assessment of peak negative dP/dt and the time constant of left ventricular isovolumic relaxation, T, before and after milrinone. In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone. After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01). Left ventricular peak filling rate increased (1.2 +/- 0.6 to 1.7 +/- 0.7 end-diastolic volumes/sec; p less than or equal to .02) despite a decrease in left ventricular filling pressure (mean pulmonary wedge pressure 27 +/- 7 to 18 +/- 9 mm Hg; p less than .01). There was a fall in left ventricular end-diastolic pressure (28.6 +/- 6 to 19 +/- 7 mm Hg; p less than or equal to .01), with no significant change in left ventricular end-diastolic volume. This was associated with a downward shift in the left ventricular diastolic pressure-volume relationship in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Milrinone: a positive inotropic vasodilator.
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Cardiotonic Agents↗
Myocardial contractile function in aortic stenosis as determined from the rate of stress development during isovolumic systole.
To assess myocardial contractile function in the chronically hypertrophied human left ventricle, the rate of stress development (dsigma/dt) as a function of developed stress (sigmaD) during isovolumic systole was examined. Results for eight patients with aortic stenosis were compared with those for seven subjects with normal left ventricular function and with those for five patients with idiopathic congestive cardiomyopathy. The rate of stress development (dsigma/dt) was nearly identical in patients with aortic stenosis and in normal subjects over a wide range of values of sigmaD but was significantly lower in patients with cardiomyopathy (P less than 0.01 versus control subjects and patients with aortic stenosis). Normal values for dsigma/dt held not only for patients with compensated pressure overload, but also for those patients with aortic stenosis with depressed left ventricular ejection fraction and overt congestive failure. Similar findings were obtained when the first derivative of left ventricular pressure (dP/dt) was examined as a function of developed left ventricular pressure in normal subjects and patients with aortic stenosis or cardiomyopathy. These results indicate that contractile function as characterized by the isovolumic rate of stress development is not necessarily impaired in chronic pressure overload hypertrophy.
Adult↗
Studies of the plasma membrane during maturation of the mammalian erythrocyte.
Plasma membranes were obtained from a homogeneous population of rabbit red blood cells at different maturation periods. Minor modifications in membrane proteins and membrane phospholipids and significant decreases in membrane glycoproteins and total lipids were observed with the age of the cell. The ouabain inhibited (Na+K+)-ATPase and the adenylate cyclase decreased with maturation but acetylcholinesterase and 5'-nucleotidase remained almost unchanged. The apparent activation energy of the ATPase increased with maturation. The results indicate that structural and functional modifications of the plasma membrane occur concomitantly with the ageing processes of the red cell.
Acetylcholinesterase↗
Association of a cyclic AMP-dependent protein kinase with a purified translational inhibitor isolated from hemin-deficient rabbit reticulocyte lysates.
In the absence of added hemin, protein synthesis in rabbit reticulocyte lysates proceeds at maximal linear rates for several minutes and then ceases abruptly. Inhibition involves the action of a translational inhibitor whose formation is regulated by hemin. Addition of the isolated inhibitor to hemin-supplemented lysates produces an inhibition of protein chain initiation similar to that observed in heme-deficiency. The inhibitor has been purified over 300-fold and contains a protein kinase activity that copurifies with the inhibitory function. With calf thymus histone II as the phosphate receptor, the inhibitor-associated protein kinase requires ATP as the phosphorylating agent. Cycle AMP stimulates kinase activity 5- to 8-fold; the concentration of cycle AMP required for halfmaximal activity is 4 X 10-8 M. Preincubation of the inhibitor in the presence of cyclic AMP significantly reduces cyclic AMP-dependent phosphorylation and inhibitory activity. The corresponding protein kinase activity from hemin-supplemented lysates displays reduced cyclic AMP-dependency and little or no inhibitory activity. These findings suggest that the protein kinase activity associated with the purified translational inhibitor is involved in the mechanism of inhibition of initiation observed in hemedeficient reticulocyte lysates.
Animals↗