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Biomedical subjects

R H Marcus

Publications and source records attributed to R H Marcus.

46 records · Page 3Linked to original sources

Clinical predictors of theophylline blood levels in asthmatic patients.

To determine the usefulness of clinical information in predicting theophylline levels, 21 parameters were studied in 204 asthmatic patients. The best single parameter for predicting theophylline levels was the last outpatient level (r = 0.484), which was within +/- 5 micrograms/mL of the presenting theophylline level in 62.5% of cases. However, there was considerable variability in theophylline levels in the other 37.5% of cases. The best combination of predictors was the last outpatient level and time since the last dose in patients taking a short-acting preparation. Even with this combination, however, 20.8% of predicted levels fell outside a range of +/- 5 micrograms/mL of the presenting theophylline levels. The only patients in whom a theophylline level could be predicted reliably were those who reported taking a sustained-release or short-acting preparation more than 15 or 8 hours prior to evaluation, respectively. In these patients, all presenting theophylline levels were in the subtherapeutic range (ie, less than 10 micrograms/mL), with 92% of the levels less than 5 micrograms/mL. Except for these patients, readily available theophylline determinations are necessary in order to optimize theophylline therapy with minimal risk of toxicity.

Adolescent↗

The upper limb-cardiovascular syndrome (Holt-Oram syndrome) in a South African family.

The upper limb-cardiovascular syndrome is reported for the first time in a South African family. There were 6 affected members in 3 generations. Infradiaphragmatic total anomalous pulmonary venous drainage, with obstruction, was found in 1 child. This rare cardiac abnormality, which constitutes only 8,5% of all cases of total anomalous pulmonary venous drainage, itself an unusual abnormality, has not previously been reported in association with the Holt-Oram syndrome.

Adult↗

Aortic stenosis and unexplained gastro-intestinal haemorrhage. Case reports.

Four cases of recurrent gastro-intestinal haemorrhage associated with aortic stenosis are described. Aortic valve replacement was accompanied by a cessation of bleeding in each patient. The source of bleeding was demonstrated or presumed to be from antral or colonic vascular ectasia. It is postulated that the altered pulse wave form in aortic stenosis may contribute towards mucosal ischaemia and ulceration in patients wtih gastro-intestinal angiodysplasia. We recommended that bowel resection be reserved for patients who continue to bleed following aortic valve replacement and who have vascular ectasia on selective mesenteric angiography.

Aged↗

Independent mechanisms for the chronotropic and inotropic responses in hyperthyroidism.

We established a hyperthyroid rat model and compared the hemodynamic responses of the hypertrophied rat heart in vivo and in vitro. Heart rate (557 +/- 26 beats/min), systolic blood pressure (162 +/- 5 mmHg) and dry heart mass (230 +/- 11 mg) in hyperthyroid rats were significantly greater than in control animals (408 +/- 12 beats/min, 140 +/- 5 mmHg and 193 +/- 4 mg respectively). In vitro studies were performed in order to eliminate neurohumoral and peripheral circulatory factors which are present in vivo. In the in vitro "working" heart preparation, there was no significant difference between the heart rates of L-thyroxine-treated (263 +/- 9 beats/min) and control (258 +/- 10 beats/min) animals, implying that the tachycardia of hyperthyroidism is partly mediated by in vivo factors. Consistent with this hypothesis was the observation that the hyperthyroid heart was more sensitive to the chronotropic effects of physiological concentrations of the synthetic catecholamine, isoproterenol (10(-8) M, 10(-7) M) than the control heart. The maximum rate of left ventricular pressure rise (dP/dtmax) was used as an index of myocardial contractility. In vitro values for dP/dtmax were significantly greater in hearts from hyperthyroid rats (5338 +/- 228 mmHg/s) than in control hearts (4583 +/- 158 mmHg/s), suggesting that the increased contractile response of hyperthyroidism is intrinsic to the heart itself. Although persistence of the inotropic response of the hyperthyroid heart in vitro was associated with an increase in heart mass, this factor alone did not account entirely for the enhanced contractility. It appears that intrinsic functional changes also contribute to the inotropic response of the hyperthyroid heart.

Animals↗

Enhanced myocardial contractility but not tachycardia persists in isolated working hyperthyroid rat hearts.

It is generally believed that the increased contractility and tachycardia of the hyperthyroid heart are a result of thyroid hormone-induced alterations of the mechanical and electrical properties of the heart, respectively. We compared the contractility (dP/dtmax) and the spontaneous beating rate of hyperthyroid and euthyroid hearts perfused in vitro in either a non-working or a working mode. The dP/dtmax (4196 +/- 74 mm Hg s-1) and beating rate (322 +/- 8 beats/min) of the non-working hyperthyroid hearts were significantly higher (p less than 0.001) than those of the euthyroid hearts (3267 +/- 115 mm Hg s-1 and 260 +/- 6 beats/min at an external Ca2+ of 2.5 mM). At 2.5 mM Ca2+, the working hyperthyroid hearts again displayed enhanced contractility (5636 +/- 179 mm Hg s-1 vs 4508 +/- 172 mm Hg s-1; p less than 0.001) but the spontaneous beating rate (275 +/- 7 beats/min) was not significantly different from euthyroid (261 +/- 8 beats/min). When hearts were subjected to periods of alternate non-working and working perfusion, the beating rate of the hyperthyroid hearts was significantly higher than euthyroid during non-working (p less than 0.02) but not during working perfusion. Increasing the afterload on the non-working preparations in a stepwise fashion from 75 cm H2O to 120 cm H2O caused significant changes in left ventricular pressure and dP/dtmax in both heart types but the tachycardia in the hyperthyroid hearts persisted (at 120 cm H2O; hyperthyroid, 294 +/- 9 beats/min; euthyroid, 224 +/- 10 beats/min; p less than 0.001). Alteration of the preload (10 to 25 cm H2O) and afterload (75 to 105 cm H2O) on working hyperthyroid and euthyroid hearts caused changes in both left ventricular pressure and dP/dtmax but the beating rates of both heart types were never significantly different. We conclude from our results that (i) the increased contractility of the hyperthyroid rat heart is due to thyroid hormone-induced alteration of the mechanical properties of the heart; (ii) the tachycardia of hyperthyroidism is not due to thyroid hormone-induced changes in the electrical properties of the heart, but probably involves some as yet unidentified chronotropic agent.

Animals↗

The role of calcium in the enhanced myocardial contractility of the hyperthyroid rat heart.

The hyperthyroid rat myocardium exhibits enhanced contractility. There is evidence that altered calcium handling by the myocardium may be responsible for this enhanced state. To investigate this, isolated hyperthyroid and euthyroid hearts were perfused in the working mode and exposed to alterations in external calcium concentration. Heart rate was not significantly different in either group of hearts, nor was it altered by the change in calcium. The concentration of calcium needed to elicit half-maximal contractility (dP/dtmax) was lower in the hyperthyroid (0.81 +/- 0.07 mM) than in the euthyroid hearts (1.12 +/- 0.09 mM, p less than 0.05). This increase in calcium sensitivity was unlikely to be at the site of the sarcolemma as verapamil exerted equal negative inotropic effects on both groups of hearts. Dantrolene, which blocks calcium release from the sarcoplasmic reticulum, exerted a significantly greater (p less than 0.01) depression in dP/dtmax after 12 min in the hyperthyroid (50 +/- 7%) than in the euthyroid heart (15 +/- 2%). We conclude from our results that the enhanced contractile state of the hyperthyroid rat heart is likely to involve an altered mechanical response to calcium which is possibly at the level of enhanced calcium release from the sarcoplasmic reticulum.

Animals↗

Double-chambered left ventricle: submitral accessory valvular tissue causing inlet and outlet obstruction.

We report a patient with a large submitral ridge of muscular and fibrous tissue that divides the left ventricle into two distinct chambers causing inlet and outlet obstruction. Doppler echocardiography revealed obstruction to both filling and ejection. Echocardiography demonstrated that the obstruction was in series with the mitral apparatus. Surgery was done with resection of much of this ring of tissue. Subsequent studies revealed morphologic and hemodynamic improvement.

Adult↗

Effect of hypoxia and catecholamine stimulation on cardiac performance in the isolated working hyperthyroid rat heart.

The hyperthyroid heart has a greater oxygen demand due to its enhanced contractile state and higher basal metabolic rate. Consequently, it may be more sensitive to conditions of decreased oxygen supply or increased oxygen use. We, therefore, investigated the effect of a restricted oxygen supply (hypoxia) and enhanced oxygen demand (catecholamine stimulation) on cardiac function in the isolated working hyperthyroid heart. Hypoxia was induced by substituting 20% of the oxygen in the perfusate with nitrogen, while catecholamine stimulation was with isoproterenol. Hypoxia caused a 37% drop in cardiac output in the hyperthyroid heart and a 10% decrease in euthyroid hearts. In response to isoproterenol, a dose-dependent increase in heart rate was found in both groups which was greatly augmented in the hyperthyroid hearts by hypoxia. With isoproterenol stimulation under normoxic conditions, euthyroid hearts showed a moderate increase in contractile performance (cardiac output and dP/dtmax), while in hyperthyroid hearts contractile performance declined. Hypoxia exacerbated the decrease in function of the hyperthyroid heart. In conclusion, our results indicate that the hyperthyroid heart is very sensitive to imbalances in the myocardial oxygen supply/demand ratio, especially when demand is increased in the presence of decreased supply.

Animals↗