Mark V. Hart

Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus

Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment, major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.

Aortic function during normal human pregnancy

Arterial rupture and dissection have been observed in both normal and complicated pregnancies. To understand how arterial mechanical properties might change during pregnancy, we measured aortic root diameter by M-mode echocardiography and obtained simultaneous cuff blood pressures during systole and diastole at rest and during isometric exercise. Measurements were obtained in 19 women at the end of normal gestation and again 3 to 6 months post partum. The aorta is larger and more compliant during normal human pregnancy, and these changes may not revert to prepregnant levels post partum. Increased aortic compliance, combined with decreased vascular resistance, may enhance left ventricular performance in normal pregnancy. Conversely, the presumed structural alterations leading to increased compliance may weaken diseased vessels leading to dissection or rupture during pregnancy.

Exercise dynamics in late gestation: Effects of physical training

Heart rate and stroke volume were measured serially in subjects at rest in the sitting position and at the onset and end of a 6-minute period of upright bicycle exercise. Twenty-three subjects with normal pregnancy were studied in late gestation and again post partum. Rest and exercise cardiac outputs in late gestation were not different from those in the postpartum period. Heart rate was higher at rest and stroke volume lower during exercise in late gestation than post partum. At the end of exercise, stroke volume fell dramatically in late gestation but not post partum. Ten women prospectively identified as physically fit had responses that were not different from those of the nonfit cohort in late gestation. Post partum, the physically fit women had exercise responses typical of trained persons and different from those of the nonfit cohort. In late gestation, rest and exercise hemodynamics in subjects in the sitting position appeared to be dominated by factors influencing venous return, independent of physical fitness.

Progesterone-induced hyperventilation in the guinea pig.

Progesterone-induced hyperventilation has thus far not been reported in animals other than humans. Accordingly we investigated the effects of chronic progesterone treatment on ventilation in guinea pigs. Virgin female guinea pigs were divided into those treated with cholesterol as controls (C), progesterone (P), or estrogen plus progesterone (E&P). All hormones were administered in silastic capsules placed subcutaneously for 28 days. On day 28 arterial blood gases and respiratory rates were determined. Arterial pH was elevated in P- and E&P-treated animals compared with controls (7.43 +/- 0.04 and 7.43 +/- 0.03 vs 7.39 +/- 0.05, respectively, P less than 0.05). Arterial PCO2 was reduced in both progesterone-treated groups compared to controls (33.9 +/- 5.8 (P), 33.1 +/- 2.8 (E&P), 38.0 +/- 4.3 (C)), and was correlated with systemic progesterone concentrations in animals receiving E&P (r = -0.85, P less than 0.01) but not in animals receiving P alone (r = -0.07, P = N.S.). Arterial [HCO-3], PO2 and respiratory rates were not different between groups. We conclude that chronic progesterone administration produces hyperventilation in guinea pigs, and that estrogen facilitates this action of progesterone.

The effects of castration and sex steroids on ventilatory control in male guinea pigs

Male guinea pigs (N = 7) given progesterone hyperventilate with PaCO2 fallings from control levels of 39.0 ± 0.6 (SEM) Torr to 32.0 ± 0.7 Torr after 7 days of treatment. This response was associated with a rise in plasma progesterone concentration to approximately 15 ng ml−1 and a transient rise in plasma 17β-estradiol concentrations. To determine the role of the testes in generating teh transient estrogen increase as well as the significance of estrogens to the progesterone response, male guinea pigs were castrated and treated either with estradiol or a placebo. Estrogen-treated castrates (N = 15) had a mean PaCO2 of 36.1 ± 0.8 Torr and the castrates given the placebo (N = 7) had an average PaCo2 of 43.8 ± 1.2 Torr (P < 0.001). Both of these castrate groups were also different from intact, untreated males (P < 0.01). Progesterone concentrations were very low and not different. When progesterone was additionally administered, the PaCO2s fell to 33.0 ± 0.8 and 38.2 ± 0.6 Torr for the estrogen- and placebo-treated castrate groups, respectively. The male guinea pig hyperventilates when given progesterone with the magnitude and time course of his response comparable to the humans. The response to progesterone is not critically dependent on the testes or on plasma estrogen concentrations; however, both castration and exogenous estrogen appear to influence PaCO2 without altering plasma progesterone concentrations.