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Biomedical subjects

R J Cody

Publications and source records attributed to R J Cody.

At least 109 records · Page 6Linked to original sources
PubMed1986

Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure.

We developed an isolated limb preparation to evaluate the direct vasoactive properties of cardioactive drugs on the forearm vasculature in patients with congestive heart failure. Using this model, we infused milrinone in subsystemic doses (1, 10, and 20 micrograms/min per 100 ml forearm volume [FAV] ) into the brachial artery of 13 patients with moderate-to-severe congestive heart failure. We monitored forearm hemodynamics, systemic hemodynamics, and milrinone plasma concentration from both the forearm venous effluent and pulmonary artery. This preparation enabled us to assess the direct forearm vascular response to milrinone. Compared with baseline forearm blood flow (2.46 +/- 1.37 ml/min/100 ml FAV), the three doses of milrinone resulted in increases in forearm blood flow to 2.66 +/- 1.43, 4.21 +/- 1.79, and 6.73 +/- 3.69 ml/min/100 ml FAV. This was associated with a reduction of forearm vascular resistance from the baseline value of 52 +/- 38 U to 47 +/- 36, 25 +/- 13, and 17 +/- 10 U. The p value for the difference in response of flow and resistance after the 10 and 20 micrograms doses vs that at baseline was .05. This forearm vasodilatation occurred without change in systemic hemodynamics or therapeutic milrinone plasma concentrations in the pulmonary artery. In five patients, we compared the response to intra-arterial milrinone with that of nitroprusside. At a dose of 10 micrograms/min/100 ml FAV, the response to nitroprusside (7.20 +/- 3.24 ml/min/100 ml FAV) was greater than that to milrinone (4.65 +/- 2.18 ml/min/100 ml FAV) (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Exercise hemodynamics and oxygen delivery in human hypertension. Response to verapamil.

To characterize the hemodynamic response to exercise and the effects of calcium channel antagonism in hypertensive subjects, invasive exercise hemodynamics were performed in the baseline state after intravenous infusion of verapamil and after 5 to 7 days of oral verapamil in 10 subjects with moderate to severe hypertension. We also assessed oxygen delivery and use and the response of the sympathetic nervous system by measuring plasma norepinephrine levels at rest and during exercise. Both routes of administration were associated with significant reductions of mean arterial pressure and systemic vascular resistance at rest and peak exercise (p less than 0.05). Changes in heart rate were not statistically significant. Following oral administration of verapamil, stroke volume increased significantly in both the resting and exercise states. Pulmonary wedge pressure did not increase; in fact, the Frank-Starling relationship of cardiac performance actually was improved. Oxygen delivery and use were unchanged with both routes of administration. There was no significant difference in rest and exercise plasma norepinephrine levels following verapamil therapy. Thus, verapamil resulted in a significant reduction of mean arterial pressure, mediated by a significant reduction of systemic vascular resistance, following both intravenous and short-term oral administration. This reduction occurred without expression of left ventricular dysfunction and was not at the expense of increased oxygen use or enhanced sympathetic nervous systemic activity.

Adult↗
PubMed1986

Sodium and water balance in chronic congestive heart failure.

As the characteristics of sodium and water balance in heart failure remain undefined, we evaluated the hemodynamic, metabolic, and hormonal effects of balanced sodium intake in 10 patients with chronic congestive heart failure. We discontinued diuretics to avoid their confounding influence, and all patients received 1 wk of 10 meq and 100 meq balanced sodium intake and controlled free water. Comparing sodium intake of 10 with 100 meq, the following observations were made. There was weight gain (2.0 kg) and increased sodium excretion (11 +/- 3 to 63 +/- 15 meq/24 h), unaccompanied by increase of blood volume. Both renin-angiotensin system and sympathetic nervous system activity were greater during the 10 meq diet, and suppressed with the 100 meq sodium diet. For both diets, plasma renin and urinary aldosterone excretion were correlated with urinary sodium excretion (r = -0.768, r = -0.726, respectively; P less than 0.005). Systemic hemodynamics were minimally changed with increased sodium intake. However, reversal of vasoconstriction by captopril during the 10 meq diet, and its ineffectiveness during the 100 meq diet, indicated a renin-dependent mechanism in the former, and a renin-independent mechanism in the latter diet. There were two subgroups of response to the 100 meq diet: one group (n = 5) achieved neutral balance, while the second (n = 5) avidly retained sodium and water. Renin-angiotensin system activity was significantly higher in the latter group, and the mechanism for differences in sodium excretion for the subgroups could not be identified by blood volume or hemodynamic parameters. Orthostatic hypotension during tilt was greater during the 10 meq sodium diet, and in all cases, related to ineffective hemodynamic and hormonal compensatory responses.

Adult↗
PubMed1986

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF.

Adult↗
PubMed1985

Acute dose range study of milrinone in congestive heart failure.

To determine the magnitude and time course of the optimal acute hemodynamic response to oral milrinone, an ascending dose range study was performed in 34 patients with severe chronic congestive heart failure (2.5 to 10 mg, n = 21; 7.5 to 15 mg, n = 13). With the 7.5- and 10-mg doses in both groups, cardiac index increased 26%, pulmonary capillary wedge pressure decreased 25% and systemic vascular resistance decreased 20%, with peak effect at 90 minutes. The hemodynamic improvement with 10 mg was sufficient to normalize cardiac index in 29% of patients. There was a clear dose-response relation, with the largest increases of cardiac index seen with the 15-mg dose (1.67 +/- 0.10 to 2.31 +/- 0.11; p less than 0.005). This dose-response relation was confirmed by the correlation of drug levels and change in cardiac index. However, some patients had significant hypotension and tachycardia with the 15-mg dose. Thus, although 10 mg appears to be optimal for most patients, the dose of milrinone should be individualized for all patients.

Administration, Oral↗
PubMed1985

Clinical and hemodynamic experience with enalapril in congestive heart failure.

The renin-angiotension system is activated in many patients with congestive heart failure (CHF), resulting in angiotensin-mediated vasoconstriction and aldosterone-mediated sodium and water retention. To evaluate the effectiveness of enalapril, a new converting enzyme inhibitor, enalapril was administered to patients either orally or intravenously in a single dose, and hemodynamic and hormonal responses were measured. Patients were then placed on oral enalapril therapy for 1 month, and treadmill exercise duration and invasive hemodynamics were compared with baseline pretreatment data. With single-dose administration, both oral and intravenous enalapril reduced systemic vascular resistance and increased cardiac output. However, the effects of oral enalapril were not manifest for 3 to 4 hours, because oral enalapril is a pro-drug form that requires hepatic deesterification. In contrast, intravenous enalapril resulted in significant hemodynamic and hormonal changes 15 to 30 minutes after administration. During long-term therapy, enalapril was associated with improved symptomatology, increase of treadmill exercise duration and sustained hemodynamic improvement. Enalapril was effective therapy for chronic CHF. Optimal short-term response may require coadministration of both intravenous and oral preparations of enalapril; however, the magnitude of the short-term response was comparable for both preparations. Long-term therapy is most effective when the drug is administered as a twice-daily regimen.

Administration, Oral↗
PubMed1985

Immediate converting-enzyme inhibition with intravenous enalapril in chronic congestive heart failure.

To test the hypothesis that intravenous enalapril is a useful pharmacologic probe of the renin angiotensin system, intravenous enalapril was administered to 9 patients with severe congestive heart failure (CHF). This produced abrupt and complete blockade of converting enzyme, with peak effect occurring at 30 minutes, as reflected by increases of plasma renin activity (from 16.8 +/- 6 to 86.6 +/- 23 ng/ml/hour) and decreases of plasma aldosterone levels (from 46 +/- 14 to 25 +/- 6 ng%) (both p less than 0.05). With reduction of angiotensin II--mediated vasoconstriction, systemic vascular resistance decreased markedly (from 1,974 +/- 233 to 1,400 +/- 136 dyne s cm-5) and cardiac index was improved (from 1.88 +/- 0.9 to 2.20 +/- 0.21 liters/min/m2) (both p less than 0.05). The time course of angiotensin II levels suggested that the lack of a cumulative effect from additive doses of intravenous enalapril was a reflection of complete inhibition of converting enzyme. One patient did not respond to enalapril; despite comparable hemodynamic severity of CHF, the renin-angiotensin system was not activated in this patient. Thus, intravenous enalapril is capable of rapid and complete inhibition of converting enzyme for the accurate assessment of angiotensin II--mediated vasoconstriction in patients with severe CHF.

Adult↗
PubMed1985

Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: prediction of mortality by ambulatory electrocardiography.

To test the hypothesis that ventricular arrhythmias detected by ambulatory electrocardiography can stratify mortality risk in patients with ischemic and those with nonischemic dilated cardiomyopathy, clinical, hemodynamic and neurohumoral findings were evaluated in 31 patients. By Kaplan-Meier analysis, the total population had 51% survival at 12 months and 19% survival at 25 months. Subgroups based on peak complexity of ventricular arrhythmias included 9 patients with simple ventricular arrhythmias (peak Lown grades 1 to 3) and 22 patients with complex ventricular arrhythmias (peak Lown grades 4 or 5). Clinical variables and baseline catecholamine levels and renin-angiotensin system activity were similar in the simple and complex arrhythmia subgroups. Patients with simple and those with complex arrhythmias were comparable by all hemodynamic indexes except for a higher mean pulmonary capillary wedge pressure in the complex arrhythmia subgroup. Survival was strikingly related to arrhythmias: mortality was 11% (1 of 9) in the simple ventricular arrhythmia subgroup and 59% (13 of 22) in the complex ventricular arrhythmia subgroup (p less than 0.025 by log-rank test). Twelve patients died suddenly and 2 patients died in circulatory failure, and the risk of death was not affected by the etiology of cardiomyopathy. The higher mortality among the patients with complex arrhythmia could not be explained by the presence of elevated filling pressures alone. Thus, ambulatory electrocardiography can stratify mortality risk among patients with severe ischemic and nonischemic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Combined hemodynamic effects of nifedipine and nitroglycerin in congestive heart failure.

To determine if the addition of preload reduction with nitrates would potentiate the acute vasodilator actions of nifedipine, we titered intravenous nitroglycerin in seven patients with severe congestive heart failure after they received a single oral dose of nifedipine. The peak hemodynamic effect of nifedipine occurred at 30 minutes, with large reductions of systemic vascular resistance (1831 +/- 128 to 1132 +/- 154 dynes X sec X cm-5; p less than 0.001) and mean arterial pressure (87 +/- 7 to 71 +/- 7 mm Hg; p less than 0.01). This was associated with an increase of stroke volume index from 22 +/- 3 to 27 +/- 3 ml/m2 (p less than 0.01) but no significant changes in heart rate, right atrial pressure, or pulmonary wedge pressure. These hemodynamic changes were attenuated over a 2-hour observation period. At 2 hours, the addition of intravenous nitroglycerin resulted in large reductions in right atrial pressure (9 +/- 2 to 6 +/- 1; p less than 0.01) and pulmonary wedge pressure (23 +/- 2 to 17 +/- 2; p less than 0.001). This was associated with further increases in cardiac index (from 1.99 +/- .15 to 2.25 +/- .14 L/min/m2; p less than 0.001) and stroke volume index (26 +/- 3 to 29 +/- 3 ml/m2; p less than 0.01). Thus, the addition of nitroglycerin to nifedipine will optimize preload reduction and enhance the vasodilator action of nifedipine. Further controlled studies are necessary to determine the long-term hemodynamic effects and the clinical role of nifedipine and its combination with nitrates in patients with severe congestive heart failure.

Adult↗
PubMed1985

Milrinone in congestive heart failure: observations on ambulatory ventricular arrhythmias.

Milrinone is a potent non-catecholamine, non-glycoside inotropic agent that can improve hemodynamic performance and functional capacity in patients with severe congestive heart failure. However, the potential effect of chronic inotropic stimulation on ventricular arrhythmias in patients with heart failure requires evaluation. We compared 24-hour ambulatory ECGs before and 2 to 4 weeks after initiation of chronic milrinone therapy in 20 patients with severe congestive heart failure (mean cardiac index 1.79 +/- 0.43 L/min/m2). A greater than tenfold increase in simple ventricular premature complex (VPC) density, a greater than tenfold increase in complex VPC form density, or an increase from 0 to greater than 5 episodes per 24 hours of any complex VPC form occurred in 35% (7 of 20) of patients. A greater than tenfold reduction in simple VPC density was noted in 5% (1 of 20), while 60% (12 of 20) of the study group had no significant change in ventricular arrhythmia profile on milrinone. The hemodynamic and functional response to milrinone, as well as entry hemodynamic profiles, were unrelated to the change in frequency or complexity of ventricular arrhythmias during therapy. Thus, milrinone therapy in congestive heart failure may be associated with the development of VPC complexity and with a significantly increased density of complex VPC forms.

Administration, Oral↗
PubMed1985

Primary muscle disease: definition of a 25-kDa polypeptide myopathic specific chagas antigen.

The sera from patients with primary heart and skeletal muscle diseases, hospitalized patients without intrinsic muscle disease from an area endemic for Trypanosoma cruzi infections, and normal subjects (N = 693) were studied for the presence of immunoglobulin G (IgG) antisarcolemma activity using serologic methods. The prevalence of elevated serum IgG antisarcolemma activity from patients with chronic Chagas' cardiomyopathy, idiopathic cardiomyopathy, polymyositis, and Duchenne muscular dystrophy was 58.9 +/- 10.4% (N = 101) (P less than 0.001 when compared to normal subjects). Two of twelve (16.7%) patients with acute T. cruzi infection and parasitemia developed elevated antisarcolemma titers, and 9/46 (19.6%) patients with chronic T. cruzi infection without evidence of cardiomyopathy yielded high antisarcolemma titers. On the other hand, patients with chronic T. cruzi infection with advanced cardiomyopathy yielded high antisarcolemma titers in 35/74 (47.3%) (P less than 0.001 when compared to normal subjects). Radioimmunoprecipitation showed a circulating antibody to a 25-kDa T. cruzi polypeptide (P25) in 16/17 (94.1%) patients with advanced cardiomyopathy and T. cruzi infection. No such antibody was shown in 12 asymptomatic subjects with chronic T. cruzi infection.

Antibodies↗
PubMed1985

Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation.

Acute and chronic hemodynamic and clinical responses to milrinone, a new oral inotrope-vasodilator agent, were evaluated prospectively in 37 patients with severe congestive heart failure. The majority of patients (n = 31) had not responded to prior vasodilator therapy, with a substantial number (n = 8) requiring intravenous inotropic support at the time of initial study. All patients showed acute hemodynamic improvement with oral milrinone, and an optimal maintenance dose was chosen for each patient during dose-ranging studies (average dose 48 mg/day). Milrinone was discontinued before follow-up hemodynamic study in 12 patients (because of worsening congestive heart failure in 6 patients, sudden death in 3 patients, arrhythmia in 1 patient and refusal by 2 patients). Hemodynamic effects of milrinone both acutely and after chronic therapy (average 37 days) were compared in the remaining 25 patients. Acutely, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 0.5 liters/min per m2 (p less than 0.001), and mean pulmonary capillary wedge pressure decreased from 28 +/- 9 to 18 +/- 8 mm Hg (p less than 0.001). When oral milrinone was readministered after chronic therapy, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 1.7 liters/min per m2 (p less than 0.001), and pulmonary capillary wedge pressure decreased from 27 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001) at 1 hour. New York Heart Association functional class improved in 18 of the 25 patients treated over a long-term period (mean 5.5 +/- 2.3 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1984

Angiotensin II-mediated vasoconstriction in chronic congestive heart failure, and response to converting enzyme inhibition.

To judge the efficacy of converting enzyme inhibitors in the management of congestive heart failure, it is necessary to interpret this in the context of the factors that stimulate renin release and the subsequent formation of angiotensin and aldosterone. The pharmacologic properties of individual converting enzyme inhibitors must be considered, and the alterations in both renin angiotensin activity and long-term converting enzyme inhibition that interact in complementary or offsetting ways to influence the long-term therapeutic result must be understood.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Estimation of angiotensin II receptor activity in chronic congestive heart failure.

The renin-angiotensin system has been shown to participate in the pathophysiology of chronic heart failure in many patients. However, the immediate assessment of this contribution in individual patients may sometimes be difficult. As a pharmacologic estimate of angiotensin II receptor activity, we infused the angiotensin II analogue, saralasin, in 20 patients with severe chronic congestive heart failure (CHF). The infusion resulted in blood pressure responses ranging from an agonist pressor response (increased systemic resistance) in patients with low intrinsic renin-angiotensin system activity, to an antagonist depressor response (decreased systemic resistance) in patients with marked activation of the renin-angiotensin system. The ability of the saralasin response to pharmacologically estimate angiotensin II receptor activity in CHF was further revealed by two physiologic maneuvers that decrease endogenous circulating angiotensin II and angiotensin II receptor occupancy. Both converting enzyme inhibition with captopril and sodium repletion, factors known to decrease endogenous angiotensin II activity, provoked agonist responses to saralasin infusion. Furthermore, saralasin was able to reverse the orthostatic hypotension precipitated by converting enzyme inhibition of angiotensin-dependent vascular tone. In summary, saralasin provided a means to estimate angiotensin receptor activity and may therefore serve as a probe of angiotensin-mediated vasoconstriction in the pathophysiology of chronic CHF.

Adult↗
PubMed1984

Haemodynamic responses to specific renin-angiotensin inhibitors in hypertension and congestive heart failure. A review.

The renin-angiotensin system is an important regulator of vascular resistance in many patients with hypertension and congestive heart failure. To quantitatively evaluate this contribution requires correlation of markers of the renin-angiotensin system with haemodynamic parameters, notably blood pressure, cardiac output, and calculated systemic vascular resistance. In addition, to determine ventricular loading properties, assessment of cardiac filling pressures is also required. The availability of specific pharmacological inhibitors of the renin-angiotensin system greatly enhances such correlation, as the haemodynamic consequence of blocking the renin-angiotensin system can then more fully identify its contribution. In the last decade, highly specific pharmacological inhibitors have become available to serve such a purpose. Renin inhibitory peptides, and renin-specific antibodies can block the rate-limiting step of the renin-angiotensin cascade: namely, the cleavage of 4 amino acids from the angiotensinogen substrate by renin. However, this method of blockade is still at the early stages of investigation. More readily available are converting enzyme inhibitors which block the formation of angiotensin II, the potent vasoconstrictor which mediates increased systemic vascular resistance, and angiotensin II analogues which compete with endogenous angiotensin II for vascular and adrenal receptors. Although hypertension and chronic congestive heart failure are clinically distinct entities in many respects, their common bond is the fact that both pathological mechanisms are mediated by an increase of systemic vascular resistance. The implications of blocking the resulting vasoconstriction in both entities are therefore quite similar. This review summarises our present knowledge of the contribution of the renin-angiotensin system to the vasoconstriction of hypertension and congestive heart failure, and also summarises the haemodynamic consequences of such inhibition. The implications of the response to these specific pharmacological probes, as well as their limitations, are discussed. Their importance rests not only in their therapeutic application, but also in their contribution as probes for pathophysiological mechanisms of vasoconstriction in cardiovascular disease.

Angiotensin II↗