Frans H.H. Leenen

Vasodilators and regression of left ventricular hypertrophy: Hydralazine versus prazosin in hypertensive humans

Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.

Exercise in children before and after coarctectomy: Hemodynamic, echocardiographic, and biochemical assessment

After repair of coarctation of the aorta, some patients with normal blood pressure at rest have an exaggerated hypertensive response to activity. Blood pressure response to exercise was studied in 15 children, aged 5 to 15 years, prior to and at periods up to 6 months following coarctectomy. Preoperatively, 11 of 15 children had systolic hypertension at rest and 12 of 15 after exercise. After surgery, only one child had mild systolic hypertension at rest, whereas exercise-induced hypertension persisted in 33% of patients (all older than 10 years). Exercise plasma renin activity was elevated preoperatively but normalized following surgery. No significant difference was seen in resting and exercise plasma catecholamine levels measured before and after surgery. Over the follow-up period of 6 months, echocardiographic evidence of left ventricular hypertrophy regressed in the younger patients but not in the older patients with exercise-induced hypertension. Exercise testing defines a subgroup of patients with exercise-induced hypertension evident soon after surgery. Structural upper segment arterial vessel wall changes in the older patient may explain these observations.

Cardiac and vascular effects of atrial natriuretic factor and sodium nitroprusside in healthy men.

To assess the contribution of venous effects to the hemodynamic changes caused by atrial natriuretic factor (ANF), the cardiac and peripheral effects of ANF were compared with those induced by the venoarterial vasodilator sodium nitroprusside. On 3 different days, eight healthy subjects received 2-hour infusions of either ANF, sodium nitroprusside, or placebo, by a single-blind crossover design. ANF was administered at a rate of 15 ng/kg/min for hour 1 and 50 ng/kg/min for hour 2; each infusion rate was preceded by a 50-micrograms bolus. The lower ANF infusion rate increased plasma cGMP fourfold, but only modest cardiovascular effects (small decreases in left ventricular end-diastolic and end-systolic volumes) were noted. At the higher ANF infusion rate, left ventricular volumes and intravascular volume, as indirectly assessed by changes in hematocrit levels, decreased further, which resulted in decreases in stroke volume, cardiac index, and systolic blood pressure. No evidence for arterial vasodilation (no decrease in diastolic blood pressure, total peripheral resistance, or forearm resistance) was obtained, and no increase in sympathetic activity was noted. In contrast, sodium nitroprusside caused arterial vasodilation, an increase in cardiac index, and significant increases in sympathetic activity. We conclude that short-term increases in plasma ANF within the physiologic range primarily affect the venous vascular bed (by decreasing intravascular volume or by venodilation) without increasing sympathetic activity.

The role of cardiac beta‐1 receptors in the hemodynamic response to a beta‐2 agonist

The role of β1‐receptors in the hemodynamic response to β2‐stimulation was assessed in seven healthy subjects by infusion of the selective β2‐agonist terbutaline both with and without selective β1‐blockade by atenolol (50 mg). Infusion of terbutaline increased heart rate (+ 28 bpm) and indices of left ventricular (LV) performance associated with a marked decrease in LV end‐systolic wall stress. The LV end‐diastolic dimension remained unchanged despite the tachycardia, suggesting that venous return had increased. Systolic blood pressure increased, whereas total peripheral resistance and diastolic blood pressure decreased. Atenolol pretreatment caused the hemodynamic changes expected of β1‐blockade but did not blunt the effects of terbutaline on heart rate, peripheral resistance, or venous return. Increases after terbutaline in LV performance and systolic blood pressure were significantly blunted by atenolol. Stimulation of β1‐receptors therefore appears to play no role in the chronotropic and only a moderate role in the inotropic response after infusion of a β2‐agonist. Alternative mechanisms for the cardiac changes with terbutaline include (1) withdrawal of vagal tone, (2) decrease in afterload, and (3) stimulation of cardiac β2‐receptors.

Cardiac effects of short term arm crank training in paraplegics: echocardiographic evidence

SummaryThe cardiac responses of male paraplegics to upper-body endurance training have been studied by M-mode echocardiography and CO2-rebreathing determination of cardiac output. Data for nine exercised subjects are compared with 5 controls. After 16 weeks of arm ergometer exercise, heart rates of trained individuals were 9 bt · min−1 lower during isometric handgrip effort (30% of MVC for 3 min), with a substantial decrease of rate pressure product (20%;p<0.05). In contrast (possibly because of greater anticipation) the control subjects developed a larger rate-pressure product with repitition of the standard isometric effort. Despite a significant increase of

Hemodynamic effects of an inhaled beta-2 agonist

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Postoperative hypertension after repair of coarctation of aorta in children: Protective effect of propranolol?

peak (19% and 31% after 8 and 16 weeks, respectively;p<0.05), echocardiographic LV mass, dimensions and indices of LV performance were unchanged by training, either at rest or during the isometric handgrip. Stroke volumes were significantly increased by 12–16% after training, both in isometric and in rhythmic work; at the highest intensity of arm ergometry, there was also a suggestion of increased cardiac output. We conclude that (1) a short period of arm training is insufficient to induce cardiac hypertrophy, (2) an increase of stroke volume with a decreased ratepressure product but no change in echocardioraphic indices of LV performance implies an improved myocardial efficiency. Possible explanations are (1) a greater strength of the trained arms, and (2) some increase of pre-loading (due to an increase of venous tone and more effective operation of the muscle pump after training).

Renal artery stenosis: An example of how the periphery can modulate voluntary alcohol drinking

Fig. 1. Composite drawing of the described wire technique. The suture wire (A) is first prepared by partial removal of a segment of the polymer coating to expose the wire proper (B), leaving the distal segment intact. This end is then inserted into the previously positioned catheter in the right ventricular cavity (C). The proximal exposed wire and skin suture wire are attached to the external pulse generator (0).