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Biomedical subjects

R J Cody

Publications and source records attributed to R J Cody.

144 records · Page 8Linked to original sources
PubMed1982

Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive heart failure: effects of acute and long-term converting-enzyme inhibition.

We assessed the hemodynamic and hormonal response to tilt and the baroreceptor response in 12 patients in sinus rhythm with severe chronic congestive heart failure. We also assessed the response to acute (n = 12) and chronic (n = 8) converting-enzyme inhibition with captopril. The control tilt was characterized by high cardiac filling pressures, absence of significant peripheral pooling and apparent absence of afferent stimuli for hemodynamic and hormonal response. After acute captopril, the hemodynamic response to tilt was improved, but not normalized. The chronic response was characterized by the absence of a reflex increase of systemic vascular resistance on tilt despite peripheral pooling. Five patients developed orthostatic hypotension, but responded to acute infusion of 0.9% sodium chloride. Efferent sympathetic activity (response to cold pressor) was abnormal during the control study, but indistinguishable from normal subjects by the time of chronic captopril therapy. This paralleled an improved responsiveness of plasma catecholamines during chronic tilt. The Valsalva maneuver remained abnormal. There was a distinct absence of the normally anticipated heart rate increase on tilt, suggesting a parasympathetic abnormality.

Adult↗
PubMed1981

Cardiovascular reflexes during long-term converting enzyme inhibition and sodium depletion. The response to tilt in hypertensive patients.

The reflex hemodynamic and humoral response to postural change during long-term renin-angiotensin blockade (captopril) was assessed in sodium-depleted hypertensive patients. Orthostatic hypotension was not observed with head-up tilt or repeated pressure recordings. During tilt, a reflex increase of heart rate occurred (76 +/- 2 to 98 +/- 4 bpm, p less than 0.001). Home recordings demonstrated only minor changes in blood pressure with standing. To evaluate these observations, hemodynamic studies were performed during tilt at three stages of therapy: control, administration of captopril, and administration of captopril plus diuretic. With tilt, no orthostatic hypotension was noted at all three stages of therapy, despite similar peripheral pooling (-22 percent cardiac index). Maintenance of blood pressure was due to reflex increase of heart rate (44, 45 and 38 percent) and systemic resistance (34, 38 and 37 percent). The response to tilt of plasma renin activity was modified by drug therapy, but not completely blocked. This study indicated that long-term converting enzyme inhibition and sodium depletion were safe and did not appreciably blunt the cardiovascular reflexes responsible for prevention of orthostatic hypotension.

Blood Pressure↗
PubMed1980

Specific inhibition of renin by an angiotensinogen analog: studies in sodium depletion and renin-dependent hypertension.

The angiotensin substrate analog Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys has no significant effect on blood pressure in sodium-replete monkeys (Macaca fascicularis) but blocks the pressor response to infused human renin. Pressor responses to angiotensin I and angiotensin II are not attenuated. In five studies in sodium-depleted monkeys, an infusion of 2 mg of the peptide per kg of body weight resulted in a reduction of mean arterial pressure (MAP) from 105 +/- 4 to 79 +/- 3 mm Hg, which is not significantly different from the response to 1 mg of the angiotensin I-converting enzyme inhibitor teprotide per kg. In uninephrectomized monkeys, inflation of a suprarenal aortic cuff caused an increase in MAP from 107 +/- 3 to 131 +/- 3 mm Hg. Infusion of 0.6 mg of the renin-inhibitory peptide per kg was followed by a return of blood pressure to 107 +/- 4 mm Hg--a depressor response similar to that observed with teprotide. This specific in vivo inhibitor of renin can now be applied to a wide variety of physiologic studies.

Angiotensin I↗
PubMed1980

M-mode echocardiography in anteroseptal myocardial infarction. Lack of sensitivity.

Eighteen patients with documented anteroseptal myocardial infarction (ASMI) were investigated with both cardiac catheterization and M-mode echocardiography. All had greater than 75% occlusion of the left anterior descending artery (LAD), proximal to the first septal perforator in 12, and distal to it in 6; 17 of 18 had abnormal septal motion by angiography. In contrast, echocardiography revealed abnormal septal motion in only 5 of 18; two others had diminished septal wall thickness in relation to posterior ventricular wall. The presence of these echocardiographic signs was not dependent either on relation of stenosis to septal perforators or on presence of septal collaterals. Although abnormal septal motion by M-mode echocardiography may indicate ASMI, normal motion does not exclude it nor does it help localize stenosis of the LAD.

Adult↗
PubMed1979

Development of antinuclear antibodies during acebutolol therapy.

Eleven patients were studied while taking the beta blocker acebutolol for a period ranging from 12 to more than 24 wk. Control titers for fluorescent antinuclear antibody (ANA) were obtained in all. Serial testing was performed over the duration of the therapy and following its discontinuation. Additional immunologic testing was performed in most patients. The patients were observed closely for the development of clinical autoimmune disease. Using a sensitive assay, fluorescent ANA developed in 8 of 9 patients with negative values in the control period. In no patient has evidence of clinical autoimmune disease developed. In general, the titers of ANA tended to rise with increasing duration of therapy and decline after its discontinuation. Positive lupus erythematosus cell preparations were also observed in several patients. These data suggest that autoantibodies are frequently induced by acebutolol and, although no evidence of clinical autoimmune disease has been reported, immunologic surveillance is warranted.

Acebutolol↗
PubMed1978

Haemodynamics of orally-active converting enzyme inhibitor (SQ 14225) in hypertensive patients.

1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension. 2. Mean arterial pressure fell (149 +/- 5 to 127 +/- 8 mmHg, P less than 0.02), because of a fall in total peripheral resistance (6.9 +/- 0.53 to 5.7 +/- 0.40 kPa 1(-1)s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 +/- 8 to 111 +/- 12 mmHg, P less than 0.05) through further resistance reduction (6.5 +/- 0.53 to 5.2 +/- 0.40 kPa 1(-1)s m2, P less than 0.05). 3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake. 4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels.

Adult↗
PubMedDate not supplied

Acute hypertension in a nonhuman primate: humoral and hemodynamic mechanisms.

The present study assessed the contribution of the renin-angiotensin system (RAS), dietary sodium, and cardiac output (CO) to the genesis of primate hypertensin in a one-kidney model which was developed to test species-specific renin inhibitors. Reduction of renal perfusion pressure increased mean arterial pressure (MAP) from 105 +/- 4 to 127 +/- 3 mm Hg (p less than 0.0005), associated with increased plasma renin activity (PRA) from 4.9 +/- 0.7 to 13.8 +/- 1.1 ng. ml-1.hr-1 (p less than 0.0005). Correlation of MAP with PRA yielded an r value of 0.662 (p less than 0.0005). Significant blood pressure elevation was obtained with both regular (R) and low sodium (LS) diet (p less than 0.0005), although the MAP change was greater with LS. With both R and LS diet, hypertension was associated with increased PRA (p less than 0.0005), and normotensive pressures were achieved with converting enzyme inhibitor (teprotide). The hemodynamic change with hypertension was an increase of systemic vascular resistance (SVR) from 0.89 +/- 0.12 to 1.17 +/- 0.09 units (p less than 0.05); cardiac output (CO) and central blood volume did not change significantly. Thus, acute hypertension, mediated by the RAS, was developed in a one-kidney primate model. The hemodynamic correlate of hypertension was increased SVR; CO and volume redistribution were not initiating factors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Plasma and platelet vasopressin in essential hypertension and congestive heart failure.

In this study we found that, in 31 normal subjects, close to 90% of circulating arginine vasopressin (AVP), measured by radioimmunoassay, was associated with platelets. By using routine methods of centrifugation, which do not completely separate platelets, the normal range of plasma vasopressin was higher by twofold than the normal range in platelet-free plasma prepared by differential centrifugation, which was 1.4 +/- 1.0 sd pg/ml. Platelet vasopressin was 12.9 +/- 5.7 pg/ml. Patients with congestive heart failure had, on average, an elevated platelet-free plasma AVP, as did two patients with thrombocytopenia and one with thrombocytosis. Patients with essential hypertension had slightly high levels of platelet-free plasma AVP and demonstrated an abnormal inverse relationship between platelet-free plasma AVP and serum osmolality. Immunoreactive platelet vasopressin was slightly low in patients with essential hypertension and was subnormal in patients with congestive heart failure. These studies demonstrate that platelets normally present in centrifuged plasma cause an overestimation of the plasma vasopressin levels. Until the physiological meaning of plasma and platelet-bound AVP is understood, studies of circulating vasopressin should probably assess both plasma and platelet AVP levels.

Arginine Vasopressin↗
PubMedDate not supplied

Renin system activity as a determinant of response to treatment in hypertension and heart failure.

In hypertension, irrespective of its underlying etiology, the baseline pretreatment renin-sodium profile predicts the antihypertensive action or the lack of it for five major types of antihypertensive drugs: 1) diuretic agents; 2) beta-receptor blockers; 3) converting-enzyme inhibitors; 4) the alpha 1 postsynaptic blocker, prazosin; and 5) the calcium channel blockers, verapamil and nifedipine. Moreover, vigorous compensatory activation of the renin-angiotensin system in response to therapy often explains initial drug ineffectiveness or resistance to treatment by diuretics and nonspecific vasodilators. This correlation between renin system behavior and antihypertensive drug efficacy likely reflect basic pharmacologic-physiologic interactions. This correlation is also observed in congestive heart failure without hypertension, where operant renin-aldosterone profiles may help to explain both drug efficacy and drug resistance to commonly administered therapeutic agents. Accordingly, a control system analysis of the renin axis has broad applications in therapy. The analysis is also conceptually significant since it exposes the operation of fundamentally different mechanisms of increased vascular resistance to flow occurring in different patients with hypertension or heart failure. One form is renin-angiotensin-mediated whereas the other, in the absence of renin, is associated with sodium-volume excess and/or abnormal alpha-adrenergic and calcium channel activity. Further definition of these two mechanisms of increased peripheral resistance could lead to a better understanding of the pathogenesis of some forms of essential hypertension and congestive heart failure.

Antihypertensive Agents↗
PubMedDate not supplied

Physiological changes due to age. Implications for drug therapy of congestive heart failure.

The segment of the population considered to be 'elderly' is consistently growing. At the same time, the number of patients with congestive heart failure continues to grow. Therefore, it is important to consider whether older patients with congestive heart failure have characteristics that identify an aging effect in addition to the obvious abnormalities produced by heart failure. Furthermore, it is important to determine the relevance of these abnormalities to the use of pharmacological therapy. Within a population of 128 consecutive heart failure patients, age-related increases of systemic vascular resistance, changes in baroreceptor responses, and increases of plasma noradrenaline (norepinephrine) levels were identified. In addition, an age-related reduction of renal function was clearly evident in patients > 65 years of age. These changes affect the use of digoxin, diuretics and angiotensin converting enzyme (ACE) inhibitors. Most notably, marked reduction of renal function in such patients must be considered in the drug treatment of heart failure.

Adult↗
PubMedDate not supplied

Clinical pharmacokinetics of the angiotensin converting enzyme inhibitors. A review.

The angiotensin converting enzyme inhibitors are an important therapeutic advance in the treatment of patients with hypertension and congestive heart failure. In addition, they are useful pharmacological probes to assess the contribution of the renin-angiotensin system to circulatory homeostasis. Captopril was the first angiotensin converting enzyme inhibitor approved for use in patients with hypertension and congestive heart failure. It is rapidly absorbed from the gastrointestinal tract, with detectable plasma concentrations apparent as early as 15 minutes. The extent of absorption is between 60 and 75% of an oral dose and peak plasma concentrations occur after approximately one hour. Captopril is primarily excreted by the kidneys via renal tubular secretion. Renal excretion is rapid, with 90% completed in the first 4 hours. The elimination half-life for unchanged captopril is about 1.7 hours and is markedly increased in the presence of renal insufficiency. Once absorbed, captopril is extensively metabolised to several forms, including a disulphide dimer of captopril, a captopril-cysteine disulphide, and other mixed disulphides with endogenous thiol compounds. It is probable that captopril and its pool of metabolites undergo reversible interconversions. Pharmacokinetic properties of captopril in patients with uncomplicated hypertension appear to be the same as in healthy subjects. However, long term administration of captopril leads to increased concentrations of total captopril, probably from the accumulation of captopril metabolites. Despite the number of potential influences on pharmacokinetic properties in patients with congestive heart failure, due to the many abnormalities in gastrointestinal tract oedema and reductions in splanchnic and renal blood flow, the available data suggest that its pharmacokinetic properties in patients with congestive heart failure resemble those in healthy subjects. However, additional data are necessary to confirm this. Enalapril is the second angiotensin converting enzyme inhibitor to become available. Enalapril is a prodrug that is well absorbed from the gastrointestinal tract, with 60 to 70% of an oral dose being absorbed. However, enalapril must be converted by hepatic esterases to the active form, enalaprilat. After the oral administration of enalapril, the tmax for enalapril is one hour, but for enalaprilat it is 4 hours. There is a prolonged terminal elimination phase with enalaprilat being detectable as late as 96 hours after dosing. Thus, enalapril has a much longer duration of action than captopril. Like captopril, enalapril is primarily excreted by the kidneys.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Early post-operative changes in left ventricular dimensions and mass following valve replacement in adults with aortic stenosis.

Twelve adults with isolated valvular aortic stenosis (AS) were evaluated for early changes of left ventricular (LV) dimensions and mass (LVM/M2) following valve replacement (AVR). M-mode echocardiography was performed pre- and 3 to 5 weeks post-AVR. LV internal diameter (LVID) decreased from 51 +/- 2.0 to 46 +/- 2.7 mm post-AVR (p less than .02). Reduction of posterior wall thickness (PWT) from 12 +/- 0.7 to 10 +/- 0.6 mm (p less than .01), interventricular septal thickness (IVST) from 13 +/- 0.9 to 11 +/- 1.2 mm (p less than .005), and mean myocardial thickness (MMT) from 12.4 +/- 0.7 to 10.5 +/- 0.7 (p less than .001), occurred post-AVR. Wall thickness/internal radius ratio was unchanged post-AVR. Calculated LVM/M2 decreased from 170 +/- 15 to 110 +/- 13 grams post-AVR (p less than .001). Normalized posterior wall velocity (PWVn) increased post-AVR from 0.66 +/- .05 to 1.08 +/- .10 sec-1 (p less than .001). For all twenty four studies, LVM/M2 and PWVn were correlated (r = -0.725, p less than .001). In summary, LV dimensions and LVM/M2 decreased significantly 3 to 5 weeks post-AVR in adults with AS. There was significant correlation of LVM/M2 and PWVn for pre-AVR and post AVR studies.

Adult↗