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Biomedical subjects

N Medina

Publications and source records attributed to N Medina.

At least 55 records · Page 3Linked to original sources
PubMed1984

Adverse hemodynamic and clinical effects of calcium channel blockade in pulmonary hypertension secondary to obliterative pulmonary vascular disease.

The hemodynamic and clinical responses to calcium channel blockade with verapamil and nifedipine were compared with those of hydralazine in 12 patients with pulmonary hypertension secondary to obliterative pulmonary vascular disease. All three drugs produced a marked and similar decrease in pulmonary vascular resistance; however, this was accompanied by a significant increase in cardiac index with hydralazine (+0.71 liter/min per m2, p less than 0.01), no change in cardiac index with nifedipine and a significant decrease in cardiac index with verapamil (-0.25 liter/min per m2, p less than 0.05). Mean pulmonary artery pressure decreased markedly with both calcium channel blocking drugs (-16.0 mm Hg with verapamil and -14.5 mm Hg with nifedipine, both p less than 0.01), but this was associated with a concomitant increase in mean right atrial pressure (+6.2 mm Hg with verapamil and +4.4 mm Hg with nifedipine, both p less than 0.01); neither variable changed after hydralazine. Hence, right ventricular performance (as reflected by right ventricular stroke work index) deteriorated during treatment with both calcium channel blocking drugs, despite the decrease in resistance to right ventricular ejection; in contrast, right ventricular stroke work index increased after hydralazine. The unfavorable hemodynamic effects of calcium channel blockade were accompanied by severe adverse clinical events, including profound hypotension and cardiogenic shock during acute drug administration and the exacerbation of right heart failure during long-term treatment. These deleterious responses to verapamil and nifedipine are likely the result of a direct depressant effect exerted by these drugs on right ventricular function independent of their pulmonary vasodilatory actions.

Adult↗
PubMed1984

Relation between serum sodium concentration and the hemodynamic and clinical responses to converting enzyme inhibition with captopril in severe heart failure.

The relation between pretreatment serum sodium concentration and the early and late effects of captopril was examined in 77 consecutive patients with severe chronic heart failure, in whom cardiac catheterization was performed during initiation of treatment and after 2 to 8 weeks. Two groups of patients were defined: 37 patients had hyponatremia (serum sodium less than 135 mEq/liter, group A) and 40 patients had a normal serum sodium concentration (greater than or equal to 135 mEq/liter, group B). With first doses of captopril, patients in group A showed more marked hemodynamic responses than did patients in group B (p less than 0.02). The changes in mean arterial pressure and left ventricular filling pressure seen with first doses of the drug varied linearly and inversely with the pretreatment serum sodium concentration (r = -0.58 and r = -0.53, respectively); this was likely related to the finding that, before administration of captopril, the serum sodium concentration varied linearly and inversely with the logarithm of the plasma renin activity (r = -0.78). However, the pretreatment serum sodium concentration did not predict the long-term hemodynamic or clinical responses to converting enzyme inhibition. Symptomatic hypotension occurred early in the course of therapy (within 24 hours of initiating captopril therapy) in 9 (12%) of the 77 patients; 8 of these 9 had severe hyponatremia (serum sodium less than 130 mEq/liter) and comprised 53% of the 15 patients in our study with such low serum sodium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Detrimental effects of verapamil in patients with primary pulmonary hypertension.

Calcium channel blockade provides a logical approach to the treatment of pulmonary hypertension because these drugs exert direct vasodilator effects in the highly constricted pulmonary circulation. To determine the effectiveness of verapamil in the treatment of primary pulmonary hypertension the haemodynamic effects of the drug were evaluated in seven patients with this disorder; 10 mg was given intravenously to six patients and 120 mg orally to one patient. Verapamil produced a 20% decline in pulmonary vascular resistance and a 27% decrease in mean pulmonary arterial pressure without significant changes in systemic vascular resistance. One patient who received verapamil 480 mg orally daily for three months showed sustained haemodynamic and clinical improvement. Concomitant with its beneficial effects on the pulmonary circulation, however, verapamil produced a pronounced decrease in right ventricular stroke work index (42%) and increase in right ventricular filling pressure (50%), indicating a direct depressant effect of the drug on right ventricular function. In one patient these cardiodepressant effects were sufficiently pronounced to produce severe hypotension and cardiac arrest. In conclusion, although verapamil appears to exert preferential vasodilator effects on the pulmonary circulation, its negative inotropic effects may be particularly detrimental to patients with primary pulmonary hypertension who have pre-existing right ventricular dysfunction; hence, treatment with verapamil is not recommended in such cases.

Adult↗
PubMed1984

Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure.

To determine the hemodynamic and clinical effects of long-term positive inotropic stimulation on the myocardium, we treated 31 patients with severe chronic heart failure with oral amrinone (600 mg daily) and performed invasive hemodynamic studies during short- and long-term treatment with the drug. Stroke volume and stroke work indexes increased markedly during the first 48 hr of therapy (p less than .01) but returned to pretreatment values after 2 to 10 weeks; upon drug withdrawal, both variables deteriorated rapidly to values significantly lower than those observed before treatment with amrinone (p less than .01), despite similar values for left ventricular filling pressure, mean arterial pressure, and systemic vascular resistance. This pattern of response indicated that progression of the underlying heart disease had occurred during treatment with amrinone and contributed importantly to its failure to produce long-term benefits. Progression of left ventricular dysfunction was associated with a progressive increase in heart rate and plasma renin activity and a decline in serum sodium concentration. Clinically, amrinone therapy was complicated by sustained symptomatic ventricular tachycardia in four patients, worsening myocardial ischemia in four patients, and worsening congestive heart failure in eight patients, all of whom had been stable before entry into the study; only three of the 31 patients improved clinically. Ten patients died during the first 2 weeks of treatment, and 16 (52%) were dead within 3 months, a mortality rate twice as great as that seen during comparable trials with vasodilating drugs. Although noncardiac adverse effects were frequent, they were not the primary reason for drug failure. In conclusion, long-term therapy with amrinone may accelerate progression of left ventricular dysfunction, exacerbate myocardial ischemia, and provoke life-threatening ventricular tachyarrhythmias, thereby shortening survival in patients with severe chronic heart failure. Prolonged administration of inotropic drugs may achieve short-term gains at the expense of long-term detrimental effects on the myocardium.

Adult↗
PubMed1984

Correction of dilutional hyponatremia in severe chronic heart failure by converting-enzyme inhibition.

To determine the effects of vasodilator and inotropic therapy on hyponatremia in patients with severe heart failure, we measured serum sodium concentration before and after treatment with captopril (70 patients), hydralazine (42 patients), prazosin (22 patients), and amrinone (19 patients), while diuretic dosages were kept constant. Serum sodium concentration increased only in hyponatremic patients treated with captopril (131.2 +/- 0.5 to 135.9 +/- 0. 5 SE ; p less than 0.001), but not during therapy with the other agents and not in patients with normal serum sodium concentration before treatment. Serum sodium began to rise 48 hours after the initiation of captopril therapy and reached its peak after 14 to 16 days. Correction of hyponatremia was related to functional interference with the renin-angiotensin system, but not to changes in renal function, serum potassium concentration, body weight, or the magnitude of hemodynamic or clinical improvement. These findings support experimental evidence that the renin-angiotensin system is important in the pathogenesis of hyponatremia in patients with severe heart failure treated with diuretics.

Adult↗
PubMed1983

Quantitative differences in the hemodynamic effects of captopril and nitroprusside in severe chronic heart failure.

The hemodynamic effects of oral captopril and intravenous nitroprusside were compared in 15 patients with severe chronic congestive heart failure. At doses of both drugs titrated so as to produce similar decreases in systemic vascular resistance in each patient, nitroprusside produced substantially greater increases in cardiac index (+0.67 versus +0.31 liters/min/m2, p less than 0.01) but smaller decreases in mean arterial pressure (-18.4 versus -11.0 mm Hg, p less than 0.01) than did captopril. This finding was due to a significant decrease in heart rate with captopril (-7 beats/min, p less than 0.01) which was not seen with nitroprusside, since changes in stroke volume index with both drugs were similar. Nitroprusside produced a decrease in pulmonary arteriolar resistance quantitatively similar to the decrease in systemic vascular resistance, but the decrease in pulmonary arteriolar resistance with captopril was not significant. Despite similar decreases in systemic resistance, captopril produced a greater decrease in left ventricular filling pressure (-10.2 versus -6.9 mm Hg, p less than 0.01) but a smaller decrease in mean right atrial pressure (-3.1 versus -5.3 mm Hg, p less than 0.01) than did nitroprusside. Thus, captopril has actions independent of its systemic vasodilator effects which account for the quantitative differences observed in its hemodynamic responses compared with those of nitroprusside in patients with severe chronic heart failure. These differences support experimental evidence that angiotensin, in addition to its direct systemic arterial vasoconstrictor actions, exerts positive chronotropic effects and alters ventricular compliance but has minimal direct effects on the limb venous circulation and on the pulmonary vasculature.

Adult↗
PubMed1983

Hemodynamic patterns of response during long-term captopril therapy for severe chronic heart failure.

To determine the relationship between the early and late hemodynamic effects of captopril in patients with severe heart failure, we performed serial right heart catheterizations in 51 such patients who were treated with the drug for 2 to 8 weeks. Four hemodynamic patterns of response were observed. Nine patients had minimal responses initially (type I); six failed to improve during long-term treatment, but three showed delayed hemodynamic benefits. Twenty-eight patients had initial beneficial drug effects that were sustained after 48 hr and after 2 to 8 weeks (type II). In seven patients, first doses of captopril produced marked beneficial responses, but these became rapidly attenuated after 48 hr; nevertheless, continued therapy for 2 to 8 weeks was accompanied by spontaneous restoration of the hemodynamic effects of first doses of the drug, i.e., triphasic response (type III). In the remaining seven patients, attenuation of initial response was not reversed by prolonged captopril therapy; hemodynamic variables after 2 to 8 weeks had returned to their pretreatment values, i.e., drug tolerance (type IV). Plasma renin activity was lower in patients with minimal responses (0.6 +/- 0.2 ng/ml/hr) and was higher in patients with triphasic responses (9.4 +/- 2.5 ng/ml/hr) than in patients with types II and IV response patterns (4.4 +/- 0.7 and 2.8 +/- 0.5 ng/ml/hr, respectively; both p less than .05). Although first-dose effects of captopril are frequently sustained, the occurrence of delayed, attenuated, and triphasic responses indicates that a complex and variable relationship may exist between the early and late hemodynamic effects of vasodilator drugs in patients with severe heart failure.

Adult↗
PubMed1982

Hemodynamic characterization of tolerance to long-term hydralazine therapy in severe chronic heart failure.

We performed hemodynamic studies in 11 patients with severe chronic heart failure whose symptoms had returned to their pretreatment status after 37 +/- 15 weeks (mean +/- S.E.M.) of therapy with the vasodilator hydralazine. The cardiac index increased from 1.85 to 3.47 liters per minute per square meter of body-surface area, and systemic vascular resistance decreased from 1748 to 754 dyn . sec. cm-5 (both p less than 0.01) during initial hydralazine administration but returned to pretreatment values on repeat evaluation; withdrawal of the drug produced no hemodynamic deterioration. Responsiveness to hydralazine could not be restored by doubling the oral dose or by intravenous administration; tolerance was associated with fluid retention in five patients but was not reversed by intensive diuresis. In contrast, the responses to nitroprusside evaluated before and after the development of hydralazine tolerance were unaltered; other oral vasodilators were still effective. We conclude that drug-specific tolerance may account for the lack of clinical improvement in some patients with severe heart failure who receive long-term treatment with hydralazine.

Adult↗
PubMed1982

Contrasting hemodynamic responses in severe heart failure: comparison of captopril and other vasodilator drugs.

Four studies were conducted in 36 patients with severe chronic heart failure to compare the central hemodynamic effects of captopril (CPT) to other vasodilator agents. While CPT produced less marked increases in cardiac output than did hydralazine (n = 14), nitroprusside (n = 15), or prazosin (n = 7), it produced decreases in left ventricular filling pressures similar to nitroprusside and prazosin but more than hydralazine. CPT and isosorbide dinitrate (n = 11) produced similar decreases in systemic vascular resistance and left ventricular filling pressure. However, cardiac output increased less with CPT than with nitrates, because heart rate slowed during CPT therapy. In addition, mean right atrial pressure decreased less with CPT than with nitrates, because CPT had minimal effects on limb venous capacitance and pulmonary arteriolar resistance. Alterations in left ventricular pressure-volume relationships likely contributed to the marked decreases in left ventricular filling pressures seen with CPT. In conclusion, the central hemodynamic effects of CPT differ significantly from other vasodilator drugs used in the treatment of heart failure patients. These effects cannot be characterized simply in terms of "balanced" peripheral arterial and venous vasodilation; CPT exerts highly complex effects on peripheral vessels as well as having actions independent of its peripheral vasodilator effects.

Adult↗
PubMed1982

Central hemodynamic effects of dipyridamole in severe heart failure: comparison with hydralazine.

The effects of dipyridamole, a coronary and peripheral vasodilator drug, on cardiac performance were investigated in nine patients with severe chronic heart failure. Dipyridamole (30 to 80 mg IV) increased cardiac index (1.63 to 2.65 l/min/m2) and decreased systemic vascular resistance (2097 to 1124 dyn/sec/cm-5). Left ventricular filling pressure decreased (23.7 to 20.7 mm Hg) without significant changes in mean right atrial pressure or heart rate. These effects were similar to the hemodynamic responses after 100 mg hydralazine in the same patients, but they were of shorter duration (less than 90 min). In contrast, oral dipyridamole induced only modest responses in three of eight patients despite large single doses of the drug (150 to 300 mg). Dipyridamole is a rapid-acting short-lived vasodilator, which exerts predominantly arterial vasodilator actions similar to those of hydralazine. Due to inconsistent response after oral doses, however, the therapeutic application of dipyridamole in long-term management of chronic heart failure appears to be limited.

Administration, Oral↗
PubMed1982

Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man.

The administration of verapamil to patients receiving beta-adrenergic blocking drugs is reported to produce adverse circulatory reactions, but a systematic investigation of this potential drug interaction has not been performed in man. We administered 40-, 80- and 120-mg doses of verapamil orally to 15 patients with angina pectoris who were receiving high doses of propranolol or metoprolol. Verapamil produced dose-dependent decreases in cardiac performance: with 120 mg, cardiac index decreased by 0.38 l/min/m2, stroke volume index decreased by 2.8 ml/beat/m2 and heart rate decreased by 6 beats/min, associated with increases in pulmonary capillary wedge (2.2 mm Hg) and mean right atrial pressures (1.7 mm Hg) (all p less than 0.01); two patients had marked, but asymptomatic, hypotensive reactions. In contrast, repeat administration of 120-mg doses of verapamil 24--30 hours after withdrawal of beta blockade produced no significant cardiodepressant effects despite significantly higher plasma levels of verapamil than during propranolol therapy (383.1 vs 205.1 ng/ml, p less than 0.01). In conclusion, verapamil produces significant negative inotropic and chronotropic effects in patients treated with beta-adrenergic antagonists; combination therapy should therefore be used with caution in patients with angina pectoris.

Adult↗
PubMed1981

Provocation of myocardial ischemic events during initiation of vasodilator therapy for severe chronic heart failure. Clinical and hemodynamic evaluation of 52 consecutive patients with ischemic cardiomyopathy.

Although hydralazine provokes myocardial ischemic events in hypertensive patients not in heart failure by producing reflex tachycardia, the frequency of and mechanisms underlying ischemic events when this drug is administered as a vasodilator agent to patients with heart failure is unknown. The responses to hydralazine in 52 consecutive patients with severe chronic heart failure secondary to coronary artery disease were reviewed. Twelve patients (23 percent) had 16 ischemic events during the initial administration of hydralazine (angina at rest in 12 and myocardial infarction in 4); these generally occurred in the absence of significant tachycardia and hypotension. Thirty-five of the 52 patients received nitroprusside (8 of whom had ischemic events with hydralazine), but this drug provoked ischemia in only 1 of the 35 although it resulted in greater decreases in systemic arterial pressure than occurred with hydralazine. In patients with ischemic event only with hydralazine, left ventricular filling pressure decreased 14.6 mm Hg with nitroprusside but only 3.9 mm Hg with hydralazine (probability [p] less than 0.01). Provocation of ischemia with hydralazine may therefore be due to the relative preservation of elevated left ventricular preload with this drug, since ischemic events are not in common with nitroprusside despite greater decreases in systemic pressures.

Adult↗
PubMed1981

Sustained effectiveness of minoxidil in heart failure after development of tolerance to other vasodilator drugs.

Although a variety of vasodilator drugs produce acute hemodynamic improvement in patients with severe chronic heart failure, long-term treatment with these agents may be associated with the development of drug tolerance and loss of initial beneficial effects. Five serial right heart catheterizations in a 78 year old man with severe chronic heart failure due to idiopathic cardiomyopathy documented the development of hemodynamic and clinical tolerance to oral hydralazine and oral captopril after initial responses were observed to both agents. However, sustained hemodynamic and clinical improvement by invasive testing was noted with minoxidil (20 mg orally twice daily) after 4 and 9 weeks of continuous therapy. These observations indicate that pharmacologic tolerance may occur with a variety of vasodilator drugs and may account for the failure of some patients to improve clinically with long-term therapy despite initial favorable hemodynamic effects. However, such tolerance seems to be drug-specific and, hence, its recognition in an individual patient does not prelude responsiveness to other vasodilator agents.

Administration, Oral↗
PubMed1981

Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.

Vasodilator drugs activate neurohumoral forces that produce peripheral vasoconstriction and tachycardia and probably cause the rebound events observed upon abrupt withdrawal of therapy. To determine their role in limiting therapeutic vasodilator responses, these reactive forces were measured in 40 patients with severe chronic heart failure by quantifying the magnitude of rebound change (MRC) after nitroprusside withdrawal. Group 1 patients (n = 22), who had minimal reactive vasoconstriction (MRC less than or equal to 27%), showed marked hemodynamic effects with nitroprusside (4.5 microgram/kg/min) and isosorbide dinitrate (40 mg orally), associated with significant decreases in heart rate with both drugs (p less than 0.001). Despite administration of the same doses of both drugs, group 2 patients (n = 18), who had marked rebound changes (MRC greater than 27%), showed significantly smaller changes in cardiac index, systemic vascular resistance and mean arterial pressure (p less than 0.001), associated with no change or increases in heart rate. Rebound events were attenuated and the responses to nitroprusside and nitrates were enhanced in four patients in whom these drugs were readministered after pretreatment with i.v. phentolamine (0.3mg/min). We conclude that activation of neurohumoral forces can limit the hemodynamic responses to vasodilator administration; this supports the use of combination therapy of direct-acting vasodilators and neurohumoral antagonists in selected patients with severe chronic heart failure.

Administration, Oral↗
PubMed1980

Importance of left ventricular chamber size in determining the response to hydralazine in severe chronic heart failure.

To examine the importance of left ventricular chamber size in determing the response to vasodilator therapy, we performed echocardiography in 40 patients with chronic refractory heart failure before they were treated with oral hydralazine. The left ventricular end-diastolic dimension (LVEDD) correlated significantly with the per cent change in stroke volume (r = 0.77), left ventricular filling pressure (r = -0.68), and stroke work index (r = 0.87) during short-term drug administration. After 14 to 21 days of maintenance therapy, 15 of 24 patients with an LVEDD greater than or equal to 60 mm were improved, and one was worse; mean blood urea nitrogen decreased from 45.6 to 30.6 mg per deciliter in the 21 patients in this group who completed the study (16.3 to 10.9 mmol per liter) (P less than 0.001). In contrast, only two of 16 patients with an LVEDD less than 60 mm improved, whereas 10 showed clinical deterioration; blood urea nitrogen increased from 49.3 to 64.2 mg per deciliter in the 13 patients in this group who completed the study (17.6 to 22.9 mmol per liter) (P less than 0.01). These findings indicate that left ventricular chamber size is an important factor in the response to hydralazine in patients with severe chronic heart failure.

Administration, Oral↗
PubMed1980

Hemodynamic evaluation of hydralazine dosage in refractory heart failure.

Hemodynamic responses to different doses of hydralazine were evaluated in 18 patients with severe refractory resistant heart failure. There were no significant overall hemodynamic effects after 50 mg hydralazine. After 75 mg, CI increased slightly (+0.36 l/min/m2) with a 19% decrease in SVR. After 100 mg, there were substantial increases in CI (+0.60 l/min/m2) and decreases in SVR (31%) changes which were greater than those after 75 mg, but the decrease in MAP with 100 mg (-6.6 mm Hg) was of the same order as that after 75 mg (-5.0 mm Hg). LVFP and SWI improved significantly only with 100-mg doses. Seven patients in whom 100 mg hydralazine induced no hemodynamic effects all responded to single doses of 150 to 200 mg. The duration of action of hydralazine was longer (p less than 0.001) in patients with a CCr less than 35 ml/min (14.3 +/- 1.4 hr) than in patients with adequate renal function (7.9 +/- 0.5 hr). Thus, the dose and dosing interval of hydralazine needed to induce hemodynamic improvement in patients with severe heart failure are variable and require individualization.

Aged↗
PubMed1979

Rebound hemodynamic events after the abrupt withdrawal of nitroprusside in patients with severe chronic heart failure.

We studied the hemodynamic events that followed abrupt withdrawal of nitroprusside in 20 patients with severe chronic heart failure. With nitroprusside, cardiac index increased from 1.96 to 2.87 liters per minute per square meter of body-surface area, but it decreased to 1.66 (P less than 0.001) after withdrawal of nitroprusside. Left ventricular filling pressure and systemic vascular resistance decreased from 23.9 to 15.3 mm Hg and from 1642 to 921 dyn.sec.cm-5, respectively, with nitroprusside, but increased to 30.4 mm Hg and 2109 dyn.sec.cm-5 (both P less than 0.001) upon its discontinuation. These rebound changes were maximal 10 to 30 minutes after nitroprusside withdrawal and returned to control levels one to three hours later. Although in 17 of 20 patients, these rebound changes caused no or minimal exacerbation of symptoms, pulmonary edema, which resolved in three patients. Activation of reflex vasoconstrictive forces during vasodilator therapy may explain these effects of withdrawal.

Adult↗