Exercise training improves endothelial function in resistance arteries of young prehypertensives.

Prehypertension is associated with reduced conduit artery endothelial function and perturbation of oxidant/antioxidant status. It is unknown whether endothelial dysfunction persists to resistance arteries and whether exercise training affects oxidant/antioxidant balance in young prehypertensives. We examined resistance artery function using venous occlusion plethysmography measurement of forearm (FBF) and calf blood flow (CBF) at rest and during reactive hyperaemia (RH), as well as lipid peroxidation (8-iso-PGF2α) and antioxidant capacity (Trolox-equivalent antioxidant capacity; TEAC) before and after exercise intervention or time control. Forty-three unmedicated prehypertensive and 15 matched normotensive time controls met screening requirements and participated in the study (age: 21.1±0.8 years). Prehypertensive subjects were randomly assigned to resistance exercise training (PHRT; n=15), endurance exercise training (PHET; n=13) or time-control groups (PHTC; n=15). Treatment groups exercised 3 days per week for 8 weeks. Peak and total FBF were lower in prehypertensives than normotensives (12.7±1.2 ml min(-1) per100 ml tissue and 89.1±7.7 ml min(-1) per 100 ml tissue vs 16.3±1.0 ml min(-1) per 100 ml tissue and 123.3±6.4 ml min(-1) per 100 ml tissue, respectively; P<0.05). Peak and total CBF were lower in prehypertensives than normotensives (15.3±1.2 ml min(-1) per 100 ml tissue and 74±8.3 ml min(-1) per 100 ml tissue vs 20.9±1.4 ml min(-1) per 100 ml tissue and 107±9.2 ml min(-1) per 100 ml tissue, respectively; P<0.05). PHRT and PHET improved humoral measures of TEAC (+24 and +30%) and 8-iso-PGF2α (-43 and -40%, respectively; P < or = 0.05). This study provides evidence that young prehypertensives exhibit reduced resistance artery endothelial function and that short-term (8 weeks) resistance or endurance training are effective in improving resistance artery endothelial function and oxidant/antioxidant balance in young prehypertensives.

Enhanced external counterpulsation improves peripheral artery function and glucose tolerance in subjects with abnormal glucose tolerance.

BACKGROUND: In coronary artery disease patients, enhanced external counterpulsation (EECP) improves peripheral arterial function and nitric oxide (NO) bioavailability, which have been implicated in the pathogenesis of abnormal glucose tolerance (AGT). We sought to evaluate the effects of EECP on outcomes of arterial function, glucose tolerance, and skeletal muscle morphology in subjects with AGT. METHODS AND RESULTS: 18 subjects with AGT were randomly (2:1 ratio) assigned to receive either 7 wk (35 1-h sessions) of EECP (n = 12) or 7 wk of standard care (control; n = 6). Peripheral vascular function, biochemical assays, glucose tolerance, and skeletal muscle morphology were evaluated before and after EECP or control. EECP increased normalized brachial artery (27%) and popliteal artery (52%) flow-mediated dilation. Plasma nitrite/nitrate (NOx) increased (30%) and 8-isoprostane-PGF-F(2α), a marker of lipid peroxidation in the plasma, decreased (-23%). Fasting plasma glucose declined (-16.9 ± 5.4 mg/dl), and the homeostasis model assessment of insulin resistance (HOMA-IR) decreased (31%) following EECP. Plasma glucose 120 min after initiation of oral glucose tolerance testing decreased (-28.3 ± 7.3 mg/dl), and the whole body composite insulin sensitivity index (C-ISI) increased (21%). VEGF concentrations increased (75%), and vastus lateralis skeletal muscle biopsies demonstrated improvements in capillary density following EECP. No change was observed in cellular signaling pathways, but there was a significant increase GLUT-4 protein expression (47%) following EECP. CONCLUSIONS: Our findings provide novel evidence that EECP has a beneficial effect on peripheral arterial function and glucose tolerance in subjects with AGT.

High-intensity dynamic human muscle performance enhanced by a metabolic intervention.

PURPOSE: The purpose of this study was to quantify the effects of a metabolic treatment on human muscle dynamic performance (strength, work, and fatigue) measured under conditions of acute, exhaustive high-intensity anaerobic isokinetic exercise. METHODS: Unilateral prefatigue and postfatigue peak torque and work values were measured in the quadriceps femoris of 13 subjects using a computer-controlled isokinetic dynamometer, over a 23-d interval. The two experimental treatments were: 1) a glycine and L-arginine salt of alpha-ketoisocaproic acid calcium ("GAKIC"); and 2) isocaloric sucrose (control). Based on a randomized double-blind cross-over repeated measures design, measurements were made before and during an exhaustive anaerobic fatigue protocol to calculate a Fatigue Resistance Index (FRI = [peri-exhaustion torque]\[baseline peak torque]), as well as total work. RESULTS: The FRI and total work for each of the exhaustion sets measured at 0, 5, and 15 min after oral GAKIC treatment were greater than values obtained for isocaloric control treatment (P < 0.02). GAKIC treatment increased the mean resistance to fatigue (FRI) up to 28% over isocaloric control. Overall gain in total muscle work attributable to GAKIC was 10.5 +/- 0.8% greater than control, sustained for at least 15 min. After 24 h, both GAKIC and control concentric forces returned to the same absolute values (P > 0.05): mean FRI = 0.42 +/- 0.05 and mean total work = 4600 +/- 280 J. There were no significant differences attributable to random order of testing. CONCLUSIONS: Compared with isocaloric carbohydrate, oral GAKIC treatment increased muscle torque and work sustained during intense acute anaerobic dynamic exercise; additionally, it increased overall muscle performance by delaying muscle fatigue during the early phases of anaerobic dynamic exercise.

Exercise following heart transplantation.

During the past 2 decades, heart transplantation has evolved from an experimental procedure to an accepted life-extending therapy for patients with endstage heart failure. However, with dramatic improvements in organ preservation, surgery and immunosuppressive drug management, short term survival is no longer the pivotal issue for most heart transplant recipients (HTR). Rather, a return to functional lifestyle with good quality of life is now the desired procedural outcome. To achieve this outcome, aggressive exercise rehabilitation is essential. HTR present unique exercise challenges. Preoperatively, most of these patients had chronic debilitating cardiac illness. Many HTR have had prolonged pretransplantation hospitalisation for inotropic support or a ventricular assist device. Decrements in peak oxygen consumption (VO2peak) and related cardiovascular parameters regress approximately 26% within the first 1 to 3 weeks of sustained bed rest. Consequently, extremely poor aerobic capacity and cardiac cachexia are not unusual occurrences in HTR who have required mechanical support or been confined to bed rest. Moreover, HTR must also contend with de novo exercise challenges conferred by chronic cardiac denervation and the multiple sequelae resulting from immunosuppression therapy. There is ample evidence that both endurance and resistance training are well tolerated in HTR. Moreover, there is growing clinical consensus that specific endurance and resistance training regimens in HTR can be efficacious adjunctive therapies in the prevention of immunosuppression-induced adverse effects and the reversal of pathophysiological consequences associated with cardiac denervation and antecedent heart failure. For example, some HTR who remain compliant during strenuous long term endurance training programmes achieve peak heart rate and VO2peak values late after transplantation that approach age-matched norms (up to approximately 95% of predicted). These benefits are not seen in HTR who do not participate in structured endurance exercise training. Rather, peak heart rate and VO2peak values in untrained HTR remain approximately 60 to 70% of predicted indefinitely. However, the mechanisms responsible for improved peak heart rate, VO2peak and total exercise time are not completely understood and require further investigation. Recent studies have also demonstrated that resistance exercise training may be an effective countermeasure for corticosteroid-induced osteoporosis and skeletal muscle myopathy. HTR who participate in specific resistance training programmes successfully restore bone mineral density (BMD) in both the axial and appendicular skeleton to pretransplantation levels, increase lean mass to levels greater than pretransplantation, and reduce body fat. In contrast, HTR who do not participate in resistance training lose approximately 15% BMD from the lumbar spine early in the postoperative period and experience further gradual reductions in BMD and muscle mass late after transplantation.

Glucocorticoid-induced osteopenia in adolescent heart transplant recipients.

BACKGROUND: Glucocorticoid-induced cushingoid symptoms, including osteopenia and osteoporosis are well-documented in adult heart transplant recipients (HTR). Bone mineral density (BMD) of the axial skeleton is diminished by 10% to 20% within 60 days after transplantation (Tx) and most adult HTR fulfill World Health Organization criteria for osteoporosis (BMD > 2.5 SD below norm). At present, we do not know whether glucocorticoids have similar deleterious effects in adolescent HTR. METHODS: To determine the consequences of glucocorticoid immunosuppression on regional bone mineral density (BMD) and biochemical markers of bone metabolism in adolescent HTR, we studied 19 patients (aged 16 +/- 3) at 19 months (group mean) after Tx. We measured BMD (hydroxyapatite g/cm(2)) of the total body, lumbar spine, and pelvis using dual-energy X-ray absorptiometry (Lunar). Serum levels of bone-specific alkaline phosphatase and pyridinoline cross-links were determined by enzyme immunoassay in serum kits. RESULTS: The BMD of the lumbar spine (-12%), femur neck (-13%), femur trochanter (-12%), and ward's triangle (-16%) were significantly (p < 0.05) lower in adolescent HTR than age- and gender-matched norms. Serum levels of alkaline phosphatase (29 +/- 6 vs 22 +/- 3 U/liter) and pyridinoline cross-links (5.3 +/- 1.1 vs 3.8 +/- 0.7 mmol/liter) were significantly (p < 0.05) elevated in adolescent HTR, compared with age- and gender-matched controls studied in our laboratory. CONCLUSIONS: Our cross-sectional results demonstrate that BMD of the axial skeleton in adolescent HTR is significantly lower (-10% to 20%) than age-matched norms and that serum biochemical markers of bone metabolism are significantly elevated, suggesting accelerated bone turnover.

High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients.

OBJECTIVES: We sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis. BACKGROUND: Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs. METHODS: Plasma volume and fluid regulatory hormones were measured in eight HTRs (57+/-6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16+/-5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated. RESULTS: Captopril pharmacologically suppressed (p<0.05) supine rest levels of angiotensin II (-65%) and aldosterone (-75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril. CONCLUSIONS: Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.

Contracted plasma and blood volume in chronic heart failure.

OBJECTIVES: The purpose of this study was to determine if long-term pharmacotherapy mediated changes in intravascular plasma and blood volumes in patients with chronic heart failure (CHF). BACKGROUND: Intravascular fluid volume expansion is an acute compensatory adaptation to ventricular dysfunction in patients with CHF. To our knowledge there are no reports on plasma and blood volume measures in clinically stable patients with CHF receiving standard pharmacotherapy. Such information may provide a better understanding of the clinical hallmarks of heart failure. METHODS: Plasma volume (PV) and blood volume (BV) were measured in 12 patients (62.8 +/- 8.2 years old, 175.2 +/- 6.8 cm, 96.2 +/- 18.2 kg, peak oxygen consumption (VO2max) 15.2 +/- 3.3 ml/kg per min) with CHF secondary to coronary artery disease (left ventricular ejection fraction 31.2 +/- 9.7, New York Heart Association functional class 2.5 +/- 0.5) and seven healthy subjects (71.7 +/- 5.3 years old, 177.1 +/- 10.8 cm, 84.4 +/- 11.7 kg, VO2max 26.0 +/- 6.5 ml/kg per min) 3 to 4 h after eating and after supine rest using the Evan's blue dye dilution technique. Venous blood samples were collected before blue dye infusion and analyzed for hematocrit (corrected 4% for trapped plasma and venous to whole body hematocrit ratio) and hemoglobin. RESULTS: Hematocrit was 36.6 +/- 3.5% and 37.4 +/- 1.1%, and hemoglobin was 15.4 +/- 1.9 and 16.2 +/- 1.4 g/dl for patients with CHF and control subjects, respectively. Absolute PV was 3489.3 +/- 655.0 and 3728.7 +/- 813.2 ml, and absolute BV was 5,496.8 +/- 1,025.4 and 5,942.4 +/- 1,182.2 ml in patients with CHF and control subjects, respectively. Relative PV was 34.1 +/- 12.9 versus 44.5 +/- 9.0 ml/kg (p < or = 0.05), and relative BV was 58.5 +/- 12.3 versus 70.8 +/- 12.6 ml/kg (p < or = 0.05) in patients with CHF and control subjects, respectively. CONCLUSIONS: Our data indicate significantly lower intravascular volumes in patients with CHF than in control subjects, indicating a deconditioned state or excessive diuresis, or both. The contracted PV and BV may contribute to exercise intolerance, shortness of breath and chronic fatigue, secondary to reduced cardiac output or regional blood flow, or both.

Rate-responsive pacing improves exercise tolerance in heart transplant recipients: a pilot study.

BACKGROUND: Chronotropic incompetence is one cause of diminished exercise capacity in heart transplant recipients. If reinnervation occurs, it often is late after transplantation and is not always accompanied by functional improvements in peak heart rate and appropriate tachycardia during exercise. To determine the efficacy of rate-responsive pacing on peak heart rate and exercise capacity, the authors studied eight male heart transplant recipients (age 57 +/- 12 years; 23 +/- 9 months after transplantation) that had either atrial or dual-chambered pacemakers. METHODS: All subjects completed two maximal graded exercise tests (GXT) using the Naughton treadmill protocol. During the first GXT, pacemakers were programmed for bradycardia support only and without rate responsiveness (unpaced). After a 14-day regimen of beta blockade with metoprolol to nullify the influence of circulating catecholamines on heart rate, subjects performed the second GXT with pacemakers programmed to respond optimally in the rate-responsive mode (paced). RESULTS: Peak heart rate (149 versus 129 bpm), peak oxygen uptake (18.9 versus 15.4 mL/kg/min), treadmill time to exhaustion (14.6 versus 12.4 min), and minute ventilation (76.7 versus 66.2 L/min) were significantly increased (P < or = 0.05) during the paced versus unpaced GXT. CONCLUSIONS: The results of this study demonstrate that chronotropic support of the transplanted heart using a rate-responsive pacemaker, with activity-based sensors programmed for maximal sensitivity, improves both peak heart rate and exercise capacity in heart transplant recipients significantly more than circulating catecholamines alone.

Neuroendocrine activation in heart failure is modified by endurance exercise training.

OBJECTIVES: The purpose of this study was to determine whether endurance exercise training could buffer neuroendocrine activity in chronic heart failure patients. BACKGROUND: Neuroendocrine activation is associated with poor long-term prognosis in heart failure. There is growing consensus that exercise may be beneficial by altering the clinical course of heart failure, but the mechanisms responsible for exercise-induced benefits are unclear. METHODS: Nineteen heart failure patients (ischemic disease; New York Heart Association [NYHA] class II or III) were randomly assigned to either a training group or to a control group. Exercise training consisted of supervised walking three times a week for 16 weeks at 40% to 70% of peak oxygen uptake. Medications were unchanged. Neurohormones were measured at study entry and after 16 weeks. RESULTS: The training group (n = 10; age = 61 +/- 6 years; EF = 30 +/- 6%) and control group (n = 9; age = 62 +/- 7 years; EF = 29 +/- 7%) did not differ in clinical findings at study entry. Resting levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the training and control groups did not differ at study entry (5.6 +/- 1.3 pg/ml; 158 +/- 38 pg/ml; 6.1 +/- 2.0 pg/ml; 37 +/- 8 pg/ml training group vs. 4.8 +/- 1.2; 146 +/- 23; 4.9 +/- 1.1; 35 +/- 10 control group). Peak exercise levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the exercise and control groups did not differ at study entry. After 16 weeks, rest and peak exercise hormone levels were unchanged in control patients. Peak exercise neurohormone levels were unchanged in the training group, but resting levels were significantly (p < 0.001) reduced (angiotensin -26%; aldosterone -32%; vasopressin -30%; atrial natriuretic peptide -27%). CONCLUSIONS: Our data indicate that 16 weeks of endurance exercise training modified resting neuroendocrine hyperactivity in heart failure patients. Reduction in circulating neurohormones may have a beneficial impact on long-term prognosis.

Exercise training in patients with CHF and heart transplant recipients.

The number of chronic heart failure (CHF) patients and heart transplantation (HT) recipients enrolled in rehabilitation and maintenance exercise programs continues to expand. There is growing clinical consensus that stable patients with CHF respond favorably to exercise training and convincing evidence that exercise training should be an essential adjunct therapy in postoperative management of HT recipients. This review examines the following specific advances in exercise physiology for heart failure and heart transplantation patients: 1) the mechanisms of exercise intolerance in CHF and the results of exercise rehabilitation studies in these patients; 2) the exercise challenges conferred by glucocorticoid therapy and chronic cardiac denervation in HT recipients; and 3) a summary of current recommendations and guidelines for exercise prescription in each patient population.

Cardiac output responses during exercise in volume-expanded heart transplant recipients.

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean +/- SD 57 +/- 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 +/- 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 +/- 12 vs 74 +/- 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p < or = 0.05) and to a greater magnitude (54 +/- 7% vs 17 +/- 4% above rest). Stroke volume at rest was lower in HT recipients (45 +/- 4 vs 68 +/- 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 +/- 0.27 vs 4.94 +/- 0.40 L/min). Relative increases in cardiac output were similar (p > or = 0.05) for the HT (106 +/- 12%) and control groups (97 +/- 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.

Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients.

PURPOSE: To determine the effect of resistance exercise training (ET) on glucocorticoid-induced myopathy in heart transplant recipients (HTR), 14 male HTR were randomly assigned to a ET group that trained for 6 months (54 +/- 3 yr old; mean +/- SD) or a control group (51 +/- 8 yr old; mean +/- SD). METHODS: Fat mass, fat-free mass, and total body mass were measured by dual-energy x-ray absorptiometry before and 2 months after transplantation (Tx), and after 3 and 6 months of ET or control period. The exercise regimen consisted of lumbar extension (MedX) performed 1 d.wk-1 and variable resistance exercises (Nautilus) performed 2 d.wk-1. PreTx body composition did not differ between groups. RESULTS: At 2 months after Tx, fat-free mass was significantly decreased below baseline in both control (-3.4 +/- 2.1%) and ET groups (-4.3 +/- 2.4%). Fat mass was significantly increased at 2 months after Tx in both the control (+8.3 +/- 2.8%) and ET groups (+7.3 +/- 4.0%). Six months of ET restored fat-free mass to levels 3.9 +/- 2.1% greater (P < or = 0.05) than before Tx. Fat-free mass of the control group decreased progressively to levels that were 7 +/- 4.4% lower than preTx values (P < or = 0.05). Both groups increased knee extension, chest press, and lumbar extensor strength, but improvements in the ET group were four- to six-fold greater (P < or = 0.05). CONCLUSION: Our results demonstrate that glucocorticoid-induced changes in body composition in HTR occur early after Tx. However, 6 months of specific ET restores fat-free mass to levels greater than before Tx and dramatically increases skeletal muscle strength. Resistance exercise, as part of a strategy to prevent steroid-induced myopathy, appears to be safe and should be initiated early after heart Tx.

Resistance exercise training restores bone mineral density in heart transplant recipients.

OBJECTIVES: This was a prospective, randomized, controlled study designed to determine the effect of resistance exercise training on bone metabolism in heart transplant recipients. BACKGROUND: Osteoporosis frequently complicates heart transplantation. No preventative strategy is generally accepted for glucocorticoid-induced bone loss. METHODS: Sixteen male heart transplant recipients were randomly assigned to a resistance exercise group that trained for 6 months (mean [+/- SD] age 56 +/- 6 years) or a control group (mean age 52 +/- 10 years) that did not perform resistance exercise. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L2 to L3) was measured by dual-energy X-ray absorptiometry before and 2 months after transplantation and after 3 and 6 months of resistance exercise or a control period. The exercise regimen consisted of lumbar extension exercise (MedX) performed 1 day/week and variable resistance exercises (Nautilus) performed 2 days/week. Each exercise consisted of one set of 10 to 15 repetitions performed to volitional fatigue. RESULTS: Pretransplantation baseline values for regional BMD did not differ in the control and training groups. Bone mineral density of the total body, femur neck and lumbar vertebra (L2 to L3) were significantly decreased below baseline at 2 months after transplantation in both the control (-3.3 +/- 1.3%, -4.5 +/- 2.8%, -12.7 +/- 3.2%, -14.8 +/- 3.1%, respectively). Six months of resistance exercise restored BMD of the whole body, femur neck and lumbar vertebra to within 1%, 1.9% and 3.6% of pretransplantation levels, respectively. Bone mineral density of the control group remained unchanged from the 2-month posttransplantation levels. CONCLUSIONS: Within 2 months after heart transplantation, approximately 3% of whole-body BMD is lost, mostly due to decreases in trabecular bone (-12% to -15% of lumbar vertebra). Six months of resistance exercise, consisting of low back exercise that isolates the lumbar spine and a regimen of variable resistance exercises, restores BMD toward pretransplantation levels. Our results suggest that resistance exercise is osteogenic and should be initiated early after heart transplantation.

Fluid homeostasis after heart transplantation: the role of cardiac denervation.

BACKGROUND: Orthotopic heart transplantation may interrupt key neural and humoral homeostatic mechanisms that normally adjust Na+ and fluid excretion to changes in intake. Such an interruption could lead to plasma volume expansion. METHODS: We measured plasma volume and fluid regulatory hormones under standardized conditions in 11 heart transplant recipients (58 +/- 7 years old; mean +/- standard deviation) 21 +/- 4 months after transplantation, in 6 liver transplant recipients (51 +/- 6 years old) 13 +/- 8 months after transplantation (cyclosporine control group), and in 7 normal healthy control subjects (61 +/- 9 years old). Administration of all diuretics and antihypertensive drugs was discontinued before the study. After 3 days during which subjects ate a constant diet containing 87 mEq of Na+ per 24 hours, plasma volume was measured by a modified Evans blue dye (T-1824) dilution technique. Renal creatinine clearance was measured and blood samples were drawn for determination of plasma levels of vasopressin, angiotensin II, aldosterone, atrial natriuretic peptide, and plasma renin activity. RESULTS: Supine resting plasma renin activity, angiotensin II, and aldosterone (renin-angiotensin-aldosterone axis) and vasopressin levels were not different among the control, heart transplant, and liver transplant groups. However, there was a trend toward elevated angiotensin II (p < or = 0.08) and aldosterone (p < or = 0.08) levels in the heart transplant recipients. Atrial natriuretic peptide levels were significantly elevated two to threefold in the heart transplant recipients when compared with those in the two control groups. Blood volume, normalized for body weight (milliliters per kilogram), was significantly greater (14%) in the heart transplant recipients when compared with that in liver transplant recipients and normal healthy control subjects. Blood volume values did not differ (p > or = 0.05) between the two control groups. CONCLUSIONS: Extracellular fluid volume expansion (+14%) occurs in clinically stable heart transplant recipients who become hypertensive. Although hyperactivity of the renin-angiotensin-aldosterone axis is not apparent during supine resting conditions, our data suggest that the renin-angiotensin-aldosterone system is not responsive to a hypervolemic stimulus and this is likely a consequence of chronic cardiac deafferentation. Thus, poor adaptation of the renin-angiotensin-aldosterone system to fluid retention may be partly responsible for the incidence and severity of posttransplantation hypertension in some heart transplant recipients.

Breakdown of blood pressure and body fluid homeostasis in heart transplant recipients.

OBJECTIVES: This study was designed to investigate disturbances in arterial blood pressure and body fluid homeostasis in stable heart transplant recipients. BACKGROUND: Hypertension and fluid retention frequently complicate heart transplantation. METHODS: Blood pressure, renal and endocrine responses to acute volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant recipients receiving similar doses of cyclosporine (cyclosporine control group) and 7 normal volunteers (normal control subjects). After 3 days of a constant diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8 ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II, aldosterone, atrial natiuretic peptide and renin activity levels were determined before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at 2 and 4 h. Blood pressure, fluid balance hormones and renal function were monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in the two control groups but increased in the heart transplant recipients (+15 +/- 8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and urinary sodium excretion increased abruptly in the control groups sufficient to account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases were blunted (p < or = 0.05) and delayed in the heart transplant recipients, resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two control groups (p < or = 0.05) but not in the heart transplant recipients. Heart transplant recipients had elevated atrial natriuretic peptide levels at baseline (p < or = 0.05), but relative increases during the infusion were similar to those in both control groups. CONCLUSIONS: Blood pressure in heart transplant recipients is salt sensitive. These patients have a blunted diuretic and natriuretic response to volume expansion that may be mediated by a failure to reflexly suppress fluid regulatory hormones. These defects in blood pressure and fluid homeostasis were not seen in liver transplant recipients receiving cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may contribute to salt-sensitive hypertension and fluid retention in heart transplant recipients.

Exercise training in patients with congestive heart failure. How to achieve benefits safely.

Inactivity adds to the decline of patients with congestive heart failure (CHF). However, in prescribing exercise in these patients, three principles must be understood: ejection fraction does not predict functional capacity, exercise can bring marked peripheral improvement without changing ejection fraction or hemodynamics, and benefits accrue slowly. The authors review the mechanisms of exercise intolerance in CHF and the factors to keep in mind when designing an exercise program.

Moderate- and high-intensity exercise lowers blood pressure in normotensive subjects 60 to 79 years of age.

To investigate the effects of exercise intensity on resting blood pressure (BP) in normotensive elderly subjects, 44 sedentary healthy subjects aged 60 to 79 years of age were studied during 6 months of walking exercise. Subjects were ranked according to maximal oxygen consumption and randomly stratified to groups that trained at 70% (n = 19) or 80% to 85% (n = 14) of maximal heart rate reserve, or to a control group (n = 11) that did not train. Initial BP was established during a 2- to 3-week control period. During the first 3 months, both exercise groups progressed to 70% of heart rate reserve for 40 minutes 3 times each week. The moderate-intensity group continued to train at 70% (45-minute duration) for an additional 3 months, whereas the high-intensity group progressed to training at 85% of heart rate reserve (35-minute duration). Maximal oxygen consumption increased (p < or = 0.05) during the initial 3 months in both exercise groups (25.2 to 28.1 ml.kg-1.min-1 and 26.3 to 29.3 ml.kg-1.min-1) and continued to increase (p < or = 0.05) after 3 additional months of training, but the increase was greater (p < or = 0.05) in the high-intensity group (28.1 to 29.4 ml.kg-1.min-1 and 29.3 to 32.8 ml.kg-1.min-1). Systolic BP decreased (p < or = 0.05) similarly at 6 months in both training groups (120 to 111 mm Hg and 120 to 112 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle strength in heart transplant recipients.

Knee extension (quadriceps) strength, peak oxygen consumption, and body composition were measured in 11 orthotopic heart transplant recipients (50 +/- 14 years of age) 18 +/- 12 months after transplantation and 11 untrained sedentary control subjects closely matched (p > or = 0.05) with respect to age, height, and weight. Peak oxygen consumption and absolute knee extension strength in the transplant recipients were 57% and 69% of control, respectively. Leg strength and peak oxygen consumption were not significantly correlated (p > or = 0.05) with months after transplantation. Peak oxygen consumption was significantly (p < or = 0.05) correlated with leg strength in both groups, but the relationship was greater in transplant recipients (r = 0.90) compared with the control group (r = 0.65). These data indicate that a leg-strength deficit persists up to 18 months after transplantation and the decrement in peak oxygen consumption observed in heart transplant recipients is partially explicable by skeletal muscle weakness. Our results underline the importance of progressive resistance training in comprehensive rehabilitation programs.

Exercise-induced hypoxemia in heart transplant recipients.

OBJECTIVES: The purpose of this study was to determine whether heart transplantation has an adverse effect on pulmonary diffusion and to investigate the potentially deleterious effects of impaired pulmonary diffusion on arterial blood gas dynamics during exercise in heart transplant recipients. BACKGROUND: Abnormal pulmonary diffusing capacity is reported in patients after orthotopic heart transplantation. Abnormal diffusion may be caused by cyclosporine or by the persistence of preexisting conditions known to adversely affect diffusion, such as congestive heart failure and chronic obstructive pulmonary disease. METHODS: Eleven patients (mean age 50 +/- 14 years) performed pulmonary function tests 3 +/- 1 months before and 18 +/- 12 (mean +/- SD) months after heart transplantation. Transplant patients were assigned to groups with diffusion > 70% (n = 5) or diffusion < 70% of predicted values (n = 5). The control group and both subsets of patients performed 10 min of cycle exercise at 40% and 70% of peak power output. Arterial blood gases were drawn every 30 s during the 1st 5 min and at 6, 8 and 10 min. RESULTS: Significant improvements in forced vital capacity (17.4%), forced expiratory volume in 1 s (11.7%) and diffusion capacity (6.6%) occurred in the patients; however, posttransplantation vital capacity, forced expiratory volume and diffusion were lower (p < or = 0.05) compared with values in 11 matched control subjects. Changes in blood gases were similar among groups at 40% of peak power output. At 70% of peak power output, arterial blood gases and pH were significantly (p < or = 0.05) lower in transplant patients with low diffusion (arterial oxygen pressure 15 to 38 mm Hg below baseline) than in patients with normal diffusion and control subjects. Cardiac index did not differ (p > or = 0.05) between transplant patients with normal and low diffusion at rest or during exercise. Posttransplantation mean pulmonary artery pressure was significantly related to exercise-induced hypoxemia (r = 0.71; p = 0.03). CONCLUSIONS: Abnormal pulmonary diffusion observed in patients before heart transplantation persists after transplantation with or without restrictive or obstructive ventilatory defects. Heart transplant recipients experience exercise-induced hypoxemia when diffusion at rest is < 70% of predicted. Our data also suggest that abnormal pulmonary gas exchange possibly contributes to diminished peak oxygen consumption in some heart transplant recipients; however, direct testing of this hypothesis was beyond the scope of the present study. This possibility needs to be investigated further.

Blood gas dynamics at the onset of exercise in heart transplant recipients.

One hypothesis to explain the rapid neural component of exercise hyperpnea contends that afferent stimuli originating in the ventricles of the heart act reflexly on the respiratory center at the onset of exercise, ie, "cardiodynamic hyperpnea." Orthotopic cardiac transplantation (Tx) results in the loss of afferent information from the ventricles. Thus, Tx possibly results in transient hypercapnia and hypoxemia in deafferented heart transplant recipients (HTR) at the onset of exercise due to hypoventilation. To examine the cardiodynamic hypothesis, we collected serial arterial blood gas (ABG) samples during both the transient and the steady-state responses to moderate cycle exercise in 5 HTRs (55 +/- 7 years) 14 +/- 7 months post-Tx and 5 control subjects matched with respect to gender, age, and body composition. Forced vital capacity, forced expiratory volume in 1 s, total lung capacity, and diffusion capacity did not differ (p > or = 0.05) between groups. Resting arterial PO2, PCO2, and pH did not differ between groups (p > or = 0.05). The ABGs were drawn every 30 s during the first 5 min and at 6, 8, and 10 min of constant load square wave cycle exercise at 40 percent of the peak power output (watts). Absolute and relative changes in arterial PO2, PCO2, and pH were similar (p > or = 0.05) between HTR and the control group at all measurement periods during exercise. Heart rate (%HRmax reserve), rating of perceived exertion, and reductions in plasma volume (% delta from baseline) did not differ between HTR and control during exercise at 40 percent of peak power output (p > or = 0.05). Our results demonstrate that there is no discernible abnormality in ABG dynamics during the transient response to exercise at 40 percent of peak power output in patients with known cardiac denervation. These data do not support the cardiodynamic hyperpnea hypothesis of ventilatory control in humans. The absence of hypercapnia in HTRs is further evidence for the existence of redundant mechanisms capable of stimulating exercise hyperpnea.