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Biomedical subjects

B M Massie

Publications and source records attributed to B M Massie.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin-converting enzyme inhibitors as cardioprotective agents.

This discussion of documented and possible cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors examines the variety of sites along the pathway to end-stage heart disease at which they might intervene. In addition to their antihypertensive activity, their effects on left ventricular hypertrophy, lipid profiles, and insulin sensitivity are discussed in comparison to the effects of other classes of antihypertensive agents on these risk factors. The ability of ACE inhibitors to prevent the progression of congestive heart failure and reduce mortality is documented and a summary of data demonstrating benefits of their use in postmyocardial infarction patients with low ejection fraction is presented.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

What is the role of silent coronary artery disease and left ventricular hypertrophy in the genesis of ventricular arrhythmias in men with essential hypertension?

Ventricular arrhythmias are not uncommon in patients with hypertension, are often attributed to left ventricular hypertrophy and are thought to be associated with an increased risk of sudden death. However, underlying silent coronary artery disease, another potential cause of ventricular arrhythmias, is often present in the same patient group. Therefore, the prevalence of ventricular arrhythmias was prospectively examined in 183 consecutive asymptomatic men with hypertension with neither clinical nor electrocardiographic (ECG) evidence of coronary artery disease in whom technically adequate echocardiograms could be obtained. After previous therapy had been withdrawn for greater than or equal to 4 days, each patient underwent exercise or dipyridamole thallium-201 scintigraphy, 48-h Holter ambulatory ECG monitoring and echocardiography for measurement of the left ventricular mass index. Forty patients (22%) had frequent ventricular ectopic activity, defined on the basis of greater than 10 premature ventricular complexes/h (38 patients) or ventricular tachycardia (11 patients), or both. A higher proportion of patients with than without a reversible thallium-201 defect had frequent premature ventricular complexes (33% vs. 18%, p less than 0.02) or ventricular tachycardia (14% vs. 4%, p less than 0.02). Similarly, more patients with than without left ventricular hypertrophy (defined as left ventricular mass index greater than or equal to 134 g/m2) had frequent premature ventricular complexes (29% vs. 15%, p less than 0.05) and ventricular tachycardia (12% vs. 2%, p less than 0.01). By stepwise logistic regression analysis, both findings were independent predictors of ventricular arrhythmia, which was present in 53% of patients with both abnormalities, but in only 12% of those with neither abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

24-hour efficacy of once-daily diltiazem in essential hypertension.

The safety and effectiveness of a once daily formulation of diltiazem hydrochloride (diltiazem CD) in the treatment of essential hypertension was assessed in a total of 127 patients with supine diastolic blood pressures (DBP) of 95 to 110 mmHg randomized to diltiazem CD (n = 61) or placebo (n = 66). Patients were titrated to doses of 120, 240, or 360 mg to achieve DBP reduction to less than 90 mmHg. At end study diltiazem CD changed trough supine SBP and DBP by -8.4 +/- 1.7 (p = 0.0009) and -8.6 +/- 1.1 mmHg (p = 0.0075), respectively. Heart rate was not significantly changed (-1.3 +/- 1.1 beats/min, p = 0.4362). The average dose of diltiazem CD was 268 mg with 69% achieving a clinical response. A subset of 47 patients underwent ambulatory blood pressure monitoring to assess the consistency of the effect over the full 24-h dosing interval. Diltiazem CD lowered DBP and SBP throughout the dosing interval. The overall side effect profile was similar to placebo. This study provides evidence of 24-h efficacy of this new, once daily formulation of diltiazem.

Adolescent↗
PubMed1992

Metabolic response of the human heart to inotropic stimulation: in vivo phosphorus-31 studies of normal and cardiomyopathic myocardium.

In order to determine if an increase in myocardial oxygen consumption is accompanied by changes in high energy phosphates in normal subjects and patients with dilated cardiomyopathy, phosphorus-31 spectra were acquired under resting conditions and during dobutamine infusion. In seven normal subjects, dobutamine raised the rate-pressure product to 226% of control. The ratio of PCr/ATP was 1.86 +/- 0.17 (mean +/- SE) under resting conditions and 1.90 +/- 0.22 (P = 0.44) with dobutamine infusion. In eight patients with dilated cardiomyopathy, dobutamine raised the rate-pressure product to 161% of control. As in the normal subjects, the ratio of PCr/ATP under resting conditions (1.63 +/- 0.24) was unchanged during dobutamine infusion (1.57 +/- 0.24, P = 0.38). These data indicate that increases in cardiac work do not have a major effect on high energy phosphate concentrations in normal subjects or in patients with clinically compensated dilated cardiomyopathy.

Adenosine Triphosphate↗
PubMed1992

Diagnostic accuracy of exercise thallium-201 scintigraphy in men with asymptomatic essential hypertension.

Coronary artery disease is responsible for much of the morbidity and mortality in patients with essential hypertension, and these complications have proven to be relatively resistant to antihypertensive therapy. However, the diagnosis of coronary disease in the hypertensive population has been considered problematic. In the present study, 30 asymptomatic patients with mild to moderate hypertension with positive exercise electrocardiograms (ECG) or stress thallium-201 scintigrams underwent coronary angiography to determine the accuracy of these tests for coronary artery disease. The exercise ECG was positive in 25 subjects, of whom 15 had significant coronary lesions and 10 did not. Thallium-201 scintigraphy proved more accurate: 17 of 18 patients with reversible abnormalities had significant obstructive coronary disease anatomically corresponding to the defect, one patient with a fixed defect had normal coronary arteries and was found to have an idiopathic cardiomyopathy, and 9 of 11 without defects had no significant lesions. The results were similar in populations with and without echocardiographic criteria for left ventricular hypertrophy. These findings indicate that despite previous suggestions to the contrary, thallium-201 scintigraphy can accurately diagnose coronary artery disease in most patients with asymptomatic essential hypertension, and that most asymptomatic hypertensive patients with physiologic evidence of myocardial ischemia have associated coronary artery disease.

Adult↗
PubMed1992

Effect of supranormal coronary blood flow on energy metabolism and systolic function of porcine left ventricle.

OBJECTIVE: The goal was to determine if supranormal coronary blood flow increases myocardial oxygen consumption, high energy phosphate levels, and systolic function in the in situ autoperfused heart. METHODS: Thirteen anaesthetised open chest pigs with an intact, autoperfused coronary circulation, weight 30-40 kg, were studied. Measurements were made under basal conditions and during regional hyperperfusion of the anterior left ventricle produced by intracoronary infusion of adenosine (mean dose 3.3 mumol.min-1). Doppler coronary blood flow velocity in the anterior descending coronary artery, arterial and anterior interventricular venous blood oxygen content, high energy phosphates (by transmurally localised 31P NMR), and myocardial wall thickening (by sonomicrometry) were measured. RESULTS: With adenosine, coronary flow was increased to 355(SEM 59)% of control. Supranormal coronary flow produced no significant changes in anterior left ventricular oxygen consumption [99(12)% of control]. 31P NMR spectroscopy revealed no significant changes in the peak intensities of phosphocreatine or ATP in either the subendocardium or subepicardium (90-97% of control). Systolic anterior left ventricular wall thickening also did not change [107(13)% of control]. CONCLUSIONS: Supranormal coronary flow does not augment myocardial oxygen consumption, high energy phosphates, or systolic function in the in situ autoperfused heart. Myocardial oxygen delivery does not limit oxidative metabolism under normal conditions.

Adenosine↗
PubMed1992

Effect of diuretic therapy on hypertensive left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) has been identified as a major independent risk factor for cardiovascular morbidity in patients with essential hypertension. It is also established that antihypertensive drug therapy is associated with regression of LVH in many patients. However, it is unclear whether all antihypertensive agents are equally effective in regressing LVH and whether this process is drug-specific or primarily related to blood pressure control. There is no universal agreement on the influence of diuretics on LVH in hypertension. Several major trials have shown consistent reversal of electrocardiographic manifestations of LVH during diuretic-based therapy. The results of studies employing echocardiographic measurements have been more variable; however, most echocardiographic studies have been flawed by lack of controls or blinding, short duration of follow-up, small sample size, inclusion of patients without LVH, and lack of consideration of previous or concomitant therapy. This review provides a critical examination of the available data on both sides of the question.

Diuretics↗
PubMed1992

Suppression of motion artifacts in fluorescence spectroscopy of perfused hearts.

Fluorescence spectroscopy of beating hearts has been used previously to measure intracellular regulators of function. Unfortunately, heart motion could introduce a spurious motion artifact (MA), influencing the measured fluorescence intensity ("signal"). To suppress MA, a ratio (or difference) has been calculated previously between the signal and an intensity reference detected at a different wavelength ("reference"). However, no studies have attempted to evaluate or optimize the efficiency of MA suppression. MA suppression was evaluated using reflected excitation light or fluorescence as reference. In addition, the MA contribution to the intensity ratio from a fluorescent dye, indo-1, was quantified. A reflected light reference resulted in poor suppression of MA. The use of a fluorescence reference resulted in suppression that was inversely related to the detection wavelength difference (delta) between the reference and signal. Therefore optimal MA suppression was obtained using a fluorescence reference at a wavelength close to the signal. For delta = 60 nm, MA was suppressed from approximately 10 to less than 2%. Finally, suppressed MA (delta = 60 nm) accounted for less than 10% of the indo-1 ratio fluctuations.

Animals↗
PubMed1992

Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo.

BACKGROUND: The functional impairment of persistently ischemic, or "hibernating," myocardium may serve to maintain myocardial cell viability through a reduction of energy requirements. Although previous studies have, in a variety of experimental models, independently shown variable responses in lactate metabolism and intracellular phosphates during prolonged ischemia, the responses of these metabolites under identical flow conditions have not been adequately described. METHODS AND RESULTS: To examine the responses of high-energy phosphates and lactate metabolism to prolonged ischemia induced by partial coronary artery stenosis, 12 open-chest pigs were studied using 31P nuclear magnetic resonance spectroscopy. Concurrent measurements of blood flow, segment shortening, high-energy phosphates, and lactate release (in nine animals) were made during 2 hours of regional ischemia. Subendocardial blood flow and segment shortening were persistently depressed during ischemia, with parallel reductions in ATP, phosphocreatine (PCr), and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Pi was persistently elevated during the ischemic period. In contrast, lactate release increased significantly from 0.23 +/- 0.04 to 1.34 +/- 0.28 mumol/ml after 15 minutes of ischemia (p less than 0.05) but then decreased to 0.73 +/- 0.17 mumol/ml at 2 hours (p less than 0.05 versus 15 minutes, p = NS versus control). Similarly, pH increased significantly from a nadir of 6.82 +/- 0.07 at 30 minutes of ischemia to 6.98 +/- 0.05 at 2 hours. CONCLUSIONS: Changes in high-energy phosphates parallel changes in blood flow and function during prolonged ischemia, whereas there is a partial amelioration in lactate production and acidosis. These data support the concept that reduction of myocardial energy requirements during prolonged flow reduction results in signs of reduced ischemia.

Animals↗
PubMed1992

Neurophysiological assessment of skeletal muscle fatigue in patients with congestive heart failure.

BACKGROUND: Recent research has demonstrated that patients with congestive heart failure (CHF) exhibit significant functional impairment of skeletal muscle and that these changes may be important determinants of exercise capacity. Although muscle strength may be mildly reduced, the most significant abnormality is markedly enhanced muscle fatigue. The goal of the present study is to determine whether accelerated fatigue is caused by impaired muscle activation, as a result of inadequate central motor drive or neuromuscular transmission, or by a change in the muscle itself. METHODS AND RESULTS: The study population consisted of nine patients with New York Heart Association class I-III CHF and eight sedentary, age- and sex-matched control subjects. Maximal voluntary contraction force of the foot dorsiflexors (primarily the tibialis anterior) was quantified as a measure of muscle strength, isometric endurance was quantified by the time required for force to decline to 60% of maximal during a sustained maximal contraction, and dynamic endurance was defined as the number of maximal contractions required for force to decline to 60% of maximal under a protocol of six repetitions per minute with an incremental duty cycle. The degree of central motor drive failure was quantified by the degree of force augmentation produced by a superimposed tetanic stimulus delivered to the peroneal nerve during the initial maximal voluntary contraction and at the time when force during the sustained isometric contraction declined to 60% of maximal. Neuromuscular junction transmission was examined by quantifying the amplitude of the compound muscle action potential (M wave) in response to a single nerve stimulus during fatiguing exercise. Muscle strength was relatively preserved in the CHF patients versus the control subjects (93 +/- 41 versus 105 +/- 34 lb; p = NS), but isometric endurance (time to decline to 60%, 34 +/- 15 versus 54 +/- 19 seconds; p less than 0.02) and dynamic endurance (number of repetitions before decline to 60%, 30 +/- 6 versus 43 +/- 7 contractions; p less than 0.001) were both impaired. Tetanic nerve stimulation increased force by similar degrees in the two groups, and the amplitude of the M wave did not decline in either group during exercise. CONCLUSIONS: These findings indicate that enhanced muscle fatigue in patients with CHF is not caused by impaired central motor drive or an abnormality of neuromuscular junction transmission but rather by an abnormality in the muscle itself.

Action Potentials↗
PubMed1992

Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts.

Coronary artery stenosis or occlusion results in reduced coronary flow and myocardial contractile depression. At severe flow reductions, increased inorganic phosphate (Pi) and intracellular acidosis clearly play a role in contractile depression. However, during milder flow reductions the mechanism(s) underlying contractile depression are less clear. Previous perfused heart studies demonstrated no change of Pi or pH during mild flow reductions, suggesting that changes of intravascular pressure (garden hose effect) may be the mediator of this contractile depression. Others have reported conflicting results regarding another possible mediator of contractility, the cytosolic free calcium (Cai). To examine the respective roles of Cai, Pi, pH, and vascular pressure in regulating contractility during mild flow reductions, Indo-1 calcium fluorescence and 31P magnetic resonance spectroscopy measurements were performed on Langendorff-perfused rat hearts. Cai and diastolic calcium levels did not change during flow reductions to 50% of control. Pi demonstrated a close relationship with developed pressure and significantly increased from 2.5 +/- 0.3 to 4.2 +/- 0.4 mumol/g dry weight during a 25% flow reduction. pH was unchanged until a 50% flow reduction. Increasing vascular pressure to superphysiological levels resulted in further increases of developed pressure, with no change in Cai. These findings are consistent with the hypothesis that during mild coronary flow reductions, contractile depression is mediated by an altered relationship between Cai and pressure, rather than by decreased Cai. Furthermore, increased Pi and decreased intravascular pressure may be responsible for this altered calcium-pressure relationship during mild coronary flow reductions.

Animals↗
PubMed1992

Skeletal muscle function, morphology, and metabolism in patients with congestive heart failure.

Work by a number of laboratories over the last decade has revealed that skeletal muscle in patients with congestive heart failure (CHF) exhibits altered metabolism, biochemistry, and histology. These alterations appear to be at least in part independent of systemic hemodynamic abnormalities and they lead to abnormal muscle function. Furthermore, muscle dysfunction may play a role in limiting exercise capacity. While blood flow to exercising muscle may be impaired in CHF, both the functional and metabolic changes are, to some degree, independent of the changes in blood flow. Deconditioning and muscle atrophy may be responsible for some of these functional metabolic alterations in muscle, but other factors appear to be operating as well. Finally, the finding that many of the changes in skeletal muscle associated with CHF can be reversed by exercise training suggests that activity should be encouraged in patients with CHF.

Exercise↗
PubMed1991

31P MRS of myocardial inorganic phosphate using radiofrequency gradient echoes.

Determination of the chemical shift and integral of the myocardial intracellular inorganic phosphate (Pi) resonance by 31P magnetic resonance spectroscopy (MRS) is often precluded due to a large overlapping signal from 2,3-diphosphoglycerate (2,3-DPG) from chamber and myocardial blood. This report demonstrates the use of radiofrequency (RF) magnetic field gradient echoes (RFGE) to eliminate signals from 2,3-DPG in flowing blood, while retaining signals from intracellular myocardial Pi, ATP, and phosphocreatine (PCr). The ECG-triggered 31P spectra were acquired from the myocardium of open chest pigs using a Philips Gyroscan 2-T magnetic resonance spectrometer. A 2.5-cm-diameter surface coil attached to the myocardium was used to provide the RF gradient as well as for excitation and detection of signals. Optimal performance of the RFGE pulse sequence was obtained when the RF gradient pulses were centered at peak diastole or peak systole. Under these conditions, 2,3-DPG signals were completely suppressed, and sensitivity was usually sufficient to allow detection of a well-resolved Pi signal. Myocardial pH determined from RFGE experiments was 7.16 +/- 0.10, and the ratio of the integrals of the Pi and ATP resonances (Pi/ATP) was 0.24. The mean signal-to-noise ratio (S/N) for PCr in control spectra acquired in 4 min was 19/1, while the mean S/N for PCr in RFGE-edited spectra acquired in 15 min was 11/1, demonstrating that the present implementation of the RFGE method results in significant loss in sensitivity. These experiments demonstrate that RFGE-editing allows accurate determination of the chemical shift and integral of the Pi resonance in blood-perfused myocardium in situ.

2,3-Diphosphoglycerate↗
PubMed1991

Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance.

In patients with congestive heart failure (CHF), the poor relationship between systemic exercise performance and cardiac function, together with morphologic and metabolic abnormalities in skeletal muscle, raises the possibility that skeletal muscle function may be impaired and limit systemic exercise performance. We assessed strength and endurance of the knee extensors during static and dynamic exercise in 16 patients with Class I-IV CHF and eight age-matched sedentary controls and related these measurements to systemic exercise performance. To assess skeletal muscle function independent of peripheral blood flow, endurance was repeated under ischemic conditions. Strength was not significantly different in the two groups. Dynamic endurance, quantified as the decline in peak torque during 15 successive isokinetic knee extensions, was significantly reduced in the patients compared to controls during aerobic (peak torque 65 vs. 86% of initial for exercise at 90 deg/s and 60 vs. 85% for exercise at 180 deg/s; P less than 0.002 for both), and during ischemic exercise (56 vs. 76% of initial torque; P less than 0.01). Static endurance, defined as the time required for force during a sustained maximal voluntary contraction to decline to 60% of maximal, was reduced in the patients compared to controls (40 +/- 14 vs. 77 +/- 29 s; P less than 0.02). There were highly significant relationships between systemic exercise performance and skeletal muscle endurance at 90 and 180 deg/s in the patients with CHF (r = 0.90 and 0.66, respectively). These findings indicate that skeletal muscle endurance is impaired in patients with CHF, that this abnormality is in part independent of limb blood flow, and that these changes may be important determinants of systemic exercise performance.

Adult↗
PubMed1991

Does the magnitude of mitral regurgitation determine hemodynamic response to vasodilation in chronic congestive heart failure?

Although it is usually assumed that direct-acting vasodilators improve cardiac function in patients with congestive heart failure (CHF) by altering left ventricular preload and afterload, several studies have suggested that most of the benefit occurs as a result of a reduction in associated mitral regurgitation (MR), which is present in the majority of patients with severe CHF. To test his hypothesis, the hemodynamic response to oral hydralazine was examined in CHF patients with competent mitral prostheses (group 1) and patients with CHF due to severe MR and left ventricular dysfunction (group 2). Both groups demonstrated significant increases in cardiac, stroke volume, and stroke work indices, although these were greater in group 2. Only group 2 experienced a significant reduction in left ventricular filling pressure. Thus, the presence of MR is not essential for hemodynamic improvement but is associated with significantly greater responses.

Adult↗
PubMed1991

Influence of therapy on silent ischemia and ventricular arrhythmias in hypertensive patients.

To assess whether therapy with hydrochlorothiazide (HCTZ) or the calcium antagonist nitrendipine influences silent ischemia or arrhythmias, we studied 10 asymptomatic hypertensive male patients with positive Tl-201 scintigraphy in a double-blind, crossover protocol. Blood pressure (BP) and 48-h Holter monitoring were obtained after 2 weeks of placebo and 8 weeks each of HCTZ and nitrendipine therapy. Ischemia was defined as greater than 1 mm ST-segment depression lasting greater than 1 min and was quantified by the number of episodes, duration, and area under the curve (AUC). The mean number of PVCs per hour and the number of episodes of ventricular tachycardia (greater than 3 beats) were also assessed. Diastolic BP was significantly reduced by both HCTZ and nitrendipine (98 +/- 6 vs. 90 +/- 6 vs. 88 +/- 7 mm Hg, respectively, p less than 0.05), but systolic BP was unchanged for either drug. The number of ischemic episodes was reduced by nitrendipine, from 2.4 +/- 3 to 0.8 +/- 2, (p less than 0.05) but not by HCTZ (2.4 +/- 3 to 1.5 +/- 3, p = NS). The duration of ischemia (37 +/- 43 vs. 5 +/- 9 min, p less than 0.05) as well as the AUC (41 +/- 45 vs. 7 +/- 14 mm/min, p less than 0.05) were reduced only by nitrendipine. The number of PVCs rose with HCTZ therapy, from 19 +/- 34 to 69 +/- 88 (p less than 0.05) and was unchanged by nitrendipine (19 +/- 34 vs. 19 +/- 40, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗