To determine whether nitric oxide contributes to the augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts, and also whether L-arginine administration can inhibit the augmented response to ET-1, we designed experiments to measure coronary perfusion resistance in isolated hearts of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with or without L-arginine administration (0.5 g/L) for 2 weeks. The hearts were paced at a constant rate and perfused by the Langendorff technique at constant pressure (75 mm Hg). Perfusion flow and pressure were monitored, and coronary vascular resistance (CVR) was calculated. ET-1 infusion elicited dose-dependent increases in CVR in both WKY and SHR. At an ET-1 concentration of 1.5 x 10(-9) mol/L, the response was significantly greater in SHR. In L-NAME-treated WKY and SHR, responses to ET-1 were augmented, compared with those of nontreated rats, and this augmentation was greater in WKY. L-arginine administration reduced the CVR response to ET-1 in SHR, whereas it did not change responses to ET-1 in WKY. These findings suggest that the augmented vasoconstriction of the coronary artery induced by ET-1 in hypertensive hearts was due to a reduction in nitric oxide release in coronary vessels and that L-arginine can partially inhibit the vasoconstrictive response of the coronary artery.

Animals↗

PubMed2000

The use of donor hearts with left ventricular hypertrophy.

BACKGROUND: We reviewed 37 patients who received donor hearts with left ventricular hypertrophy (LVH) to determine which factors affected outcomes. METHODS: Thirty-seven patients underwent orthotopic heart transplantation (1994 through 1998) with donor hearts qualified as having LVH by echocardiography (EC) and/or electrocardiogram (ECG). We performed univariate analysis on 18 donor and recipient risk factors for mortality. We calculated 12-month survival curves using Kaplan-Meier estimates and compared them using the log-rank test. A contemporaneous cohort of 221 patients who received optimal hearts within the same institution served as a control for survival. RESULTS: Median follow-up was 18 months (1 to 53). Median recipient age was 58 ye ars (25 to 75), and median donor age was 47 years (12 to 63). Median donor/recipient height and weight ratios were 1.01 (0.9 to 1.19) and 1.16 (0.77 to 2.02), respectively. Two-month survival was 86.4%, and 12-month survival was 73.0%. Survival for the control group was 91. 6% at 2 months and 86.9% at 12 months. Clinically inferior survival curves were observed when donors had known hypertension (n = 17, 95% vs 71% at 2 months, 76% vs 65% at 12 months), ischemia > 180 minutes (n = 18, 95% vs 72% at 2 months, 78% vs 65% at 12 months), LVH by ECG (n = 10, 85% vs 80% at 2 months, 77% vs 56% at 12 months), and greater than mild or unknown ECHO grade (n = 18, 89% vs 72% at 2 months, 84% vs 59% at 12 months, p = 0.11). CONCLUSIONS: Donor hearts with mild LVH may be used selectively, particularly if there are no ECG criteria and if ischemia time is short. Caution is indicated for donors with documented history of hypertension. Precise measurement of LV wall thickness by EC is needed in all donors to estimate severity and to complement ECG interpretation.

Adolescent↗

PubMed2000

Sixteen-year experience with 1,000 heart transplants at UCLA.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Adolescent↗

PubMed1999

Sustained-release diltiazem overdose.

Explore the source record for details and available documents.

Calcium Channel Blockers↗

PubMed1999

Central effects of endothelin and its antagonists on sympathetic and cardiovascular regulation in SHR-SP.

Intracerebroventricular injections of endothelin-1 (ET-1) are reported to cause dose-related increases in sympathetic nerve activity and blood pressure in anesthetized normotensive rats. These studies were performed to determine the following: which endothelin receptor, A or B, is involved in mediating sympathetic and cardiovascular effects of ET-1 injected centrally; whether central endothelin tonically participates in blood pressure regulation in normotensive rats; and whether the altered endothelin system in the central nervous system contributes to blood pressure elevation in hypertensive rats. ET-1, ET-A antagonist (BQ-123), or ET-B antagonist (RES-701-1) was injected into the lateral cerebral ventricle (i.c.v.) of urethane-anesthetized normotensive Wistar and Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs), and stroke-prone SHRs (SHR-SPs). In Wistar rats, i.c.v. injections of ET-1 (1, 5, 10 pmol) consistently increased sympathetic nerve activity, thereby elevating blood pressure in a dose-related manner. The pressor responses induced by i.c.v. ET-1 were abolished after intravenous pretreatment with phentolamine. Neither ET-A nor ET-B antagonist, when injected centrally, altered basal levels of sympathetic nerve activity, heart rate, or blood pressure in Wistar rats. However, sympathetic activation and pressor responses induced by i.c.v. injection of endothelin were completely abolished after i.c.v. pretreatment with ET-A antagonist but were unaffected after pretreatment with ET-B antagonist. Although i.c.v. injections of ET-1 increased sympathetic nerve activity and blood pressure in WKY rats, SHRs, and SHR-SPs, the magnitudes of these responses did not differ among these three groups. In contrast, i.c.v. injections of ET-A antagonist decreased sympathetic nerve activity, blood pressure, and heart rate only in SHR-SPs, but not in WKY rats and SHRs. In addition, the depressor effects of i.c.v. ET-A antagonist in SHR-SPs were ascertained while these rats were awake. In summary, i.c.v. injections of ET-1 increased sympathetic nerve activity and blood pressure via ET-A receptors but not via ET-B receptors. Central ET might tonically activate sympathetic nerve activity to thereby contribute to blood pressure elevation in SHR-SPs, but not in WKY rats and SHRs.

Anesthesia↗

PubMed1998

Unique association of pheochromocytoma with contralateral nonfunctioning adrenal cortical adenoma.

A 57-year-old woman complaining of hypertensive attacks associated with headache and palpitation was admitted to our hospital for examination of bilateral adrenal tumors in 1985. After right pheochromocytoma was diagnosed, right adrenalectomy was performed. The left adrenal tumor was small; thus, the left adrenal tumor was preserved to avoid adrenal insufficiency, although left adrenal pheochromocytoma could not be denied. In 1995, she was referred to our clinic again because of recurrent headache and palpitation, and enlargement of the left adrenal tumor. Although pheochromocytoma was suspected again, the enlarged left adrenal turned out to be a nonfunctioning cortical adenoma. This case was interesting, not only because of difficulty in identifying the left adrenal tumor, but also because of the rare coexistence of a pheochromocytoma and a nonfunctioning adrenal cortical tumor.

Adrenal Cortex Neoplasms↗

PubMed1998

Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.

To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.

Angiotensin II↗

PubMed1997

Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR.

We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.

Animals↗

PubMed1997

Impact of a comprehensive heart failure management program on hospital readmission and functional status of patients with advanced heart failure.

OBJECTIVES: To assess the impact of a comprehensive heart failure management program, functional status, hospital readmission rate and estimated hospital costs were determined and compared for the 6 months before and the 6 months after referral. BACKGROUND: The course of advanced heart failure is characterized by progressive clinical deterioration reflected in frequent hospital admissions, which comprise the major financial cost. METHODS: Over a 3-year period, 214 patients were accepted for heart transplantation and discharged after evaluation, which included adjustments in medical therapy and intensive patient education. Patients were in New York Heart Association functional class III or IV (94 and 120 patients, respectively), with a mean left ventricular ejection fraction of 0.21, peak oxygen consumption of 11 ml/kg per min and a total of 429 hospital admissions in the previous 6 months (average 2.0 per patient). Changes in the medical regimen included a 98% increase in angiotensin-converting enzyme inhibitor dose and a flexible diuretic regimen after 4.2-liter net diuresis, with counseling also regarding diet and progressive exercise. RESULTS: During the 6 months after referral, there were only 63 hospital readmissions (85% reduction), with 0.29/patient (p < 0.0001). Functional status improved as assessed by functional class (p < 0.0001) and peak oxygen consumption (15.2 vs. 11.0 ml/kg per min, p < 0.001). The same results were seen after excluding the 35 patients without full 6-month follow-up (9 deaths, 14 urgent transplant procedures during hospital readmission, 12 elective transplant procedures from home); 34 hospital admissions occurred after referral, compared with 344 before referral. Even when adding in the initial hospital admission after referral for these 179 patients, there was a 35% decrease in total hospital admissions in the 6-month period. The estimated savings in hospital readmission costs after subtracting the initial hospital costs for management was $9,800 per patient. CONCLUSIONS: Comprehensive heart failure management led to improved functional status and an 85% decrease in the hospital admission rate for transplant candidates discharged after evaluation. The potential to reduce both symptoms and costs suggests that referral to a heart failure program may be appropriate not only for potential heart transplantation, but also for medical management of persistent functional class III and IV heart failure.

Comprehensive Health Care↗

PubMed1997

The alternate recipient list for heart transplantation: does it work?

BACKGROUND: One quarter of patients awaiting heart transplantation die while on the waiting list. This is largely due to the shortage of donor organs. The alternate recipient list was created to establish a means by which patients who would otherwise be turned down for heart transplantation solely because of age over 65 or a need for a third heart transplantation can receive organs considered marginal that may otherwise be wasted. The hope is that these patients may achieve improved survival with these substandard hearts than they would achieve with medical therapy alone. METHODS: Twenty-two patients ages 47 to 71 years (mean 66.7 years) were listed on the alternate recipient list at the University of California at Los Angeles Medical Center from 1991 to 1996. Seventeen patients underwent heart transplantation from the alternate waiting list. The outcome of this group was compared with the outcome of a contemporaneous group of 266 patients ages 18 to 66 years (mean age 52.1 years) from the standard heart transplantation waiting list. RESULTS: The early mortality rate for the patients in the alternate group was 11.8% (2/ 17). Actuarial survival from time of orthotopic heart transplantation at 6 months and 1 year was the same 74.5% at a mean follow-up was 13.4 months. In comparison, the early mortality rate for the patients on the standard list was 5.6% (15/266), and actuarial survival at 6 months and 1 year was 86.8% and 83.1%, respectively (mean follow-up was 30 months). There was no significant difference in early mortality rate or actuarial survival between the two groups. CONCLUSION: The alternate recipient list for heart transplantation is a valid and ethical option for patients who would otherwise be denied heart transplantation. It provides these patients with similar early and medium-term outcomes in comparison to patients on the standard list, and organs that may otherwise be wasted are used.

Adolescent↗

PubMed1996

Outcomes of patients undergoing transplantation with older donor hearts.

BACKGROUND: The limited number of donor hearts relative to the number of waiting recipients is the major determinate of a growing inequity. Although a number of potential options are being vigorously pursued, the most effective immediate solution is to expand acceptance criteria for donor age and medical condition. This report is a review of our early and late results with the use of older donors, including simultaneously "bypassed" donor hearts. METHODS: Between April 1987 and September 1994, 52 patients received older donor hearts (older than 45 years) with a mean donor age of 51 years. Ten patients in this group received hearts simultaneously bypassed with from 1 to 4 grafts per patient. Donor and recipient age, diagnosis, and HLA match were compared between the older donor group and a contemporaneous younger (younger than 45) donor group (N = 324). Also compared was actuarial survival at up to 5 years of follow-up in addition to graft function, bypass graft patency, infection and rejection incidence at 1 year, and the prevalence of transplant-associated coronary artery disease in the two groups. Echocardiography, coronary angiography, and intravascular coronary ultrasonography were used for this assessment. RESULTS: One-year actuarial survival was 84% for the older donor group, which included 19 status 1 patients (survival 76%) and 23 status II patients (survival 90%). In the bypassed donor subgroup there was a 60% 1-year actuarial survival with 5 status 1 patients (survival 80%) and 5 status II patients (survival 40%). At 1 year, left ventricular function and the incidence of infection and rejection were equal between these two donor groups. Five-year actuarial survivals were the same between the overall older and younger donor groups. Finally, the development of transplant-associated coronary disease was similar in both groups up to 5 years after transplantation. CONCLUSIONS: This initial review of heart transplantation with older donor hearts, including bypassed hearts, demonstrates similar early and late survival outcomes as compared with those of a contemporaneous younger donor group. Significantly, there appears to be no difference in the development of transplant-associated coronary artery disease during the follow-up period. The older donor represents a potential immediate increase in the number of suitable hearts for transplantation. Bypassed donor hearts represent a small but potentially significant subgroup that may be safely and effectively used when appropriately matched to the recipient by age and medical condition. Greater experience, particularly with this bypassed group, will help determine optimal donor-to-recipient matching for the future.

Adult↗

PubMed1993

[Two cases of anomalous origin of coronary artery from non-coronary sinus of valsalva identified by transesophageal echocardiography].

A 36-year-old male (case-1) and a 54-year-old female (case-2) were admitted to our hospital because of chest oppression on effort. Exercise electrocardiograms of both patients revealed significant ST segment depression in leads II, III, aVF and V5-6. Coronary angiograms demonstrated an anomalous origin of the left circumflex coronary artery in case-1 and an anomalous origin of the right coronary artery in case-2. Furthermore transesophageal echocardiography (TEE) revealed that both anomalous coronary arteries were running from the non-coronary sinus of Valsalva. The anatomical relation between the anomalous coronaries running from non-coronary sinus of valsalva and the great vessels was directly detectable by TEE. Although these cases are very rare, TEE is useful for the assessment of this type of coronary anomaly.

Adult↗

PubMed1992

Amiodarone therapy does not compromise subsequent heart transplantation.

OBJECTIVES: The objective of this study was to determine the frequency of pulmonary complications, feasibility of early hospital discharge and requirements for postoperative inotropic and chronotropic support in patients receiving amiodarone therapy before heart transplantation. BACKGROUND: Although many patients waiting for heart transplantation will die of arrhythmias before a donor heart is found, the use of amiodarone has been limited by concern about increased complications in the perioperative period. METHODS: The 29 patients receiving amiodarone at the time of heart transplantation at University of California, Los Angeles Medical Center between October 1986 and September 1990 were compared with 29 control recipients to evaluate postoperative morbidity. Patients were receiving amiodarone for recurrent ventricular tachyarrhythmias (n = 11), atrial fibrillation (n = 2) or complex ventricular ectopic activity (n = 16). The average daily dose was 360 +/- 230 mg/day for an average of 11 +/- 22 months before transplantation. Amiodarone and control groups had a similar ejection fraction (0.18 +/- 0.07 vs. 0.20 +/- 0.08), frequency of coronary disease, age and gender. There were three more status I patients in the control group. OKT3 was given to only two patients receiving amiodarone and 12 control patients at high risk for renal dysfunction. RESULTS: Postoperatively, the duration of assisted ventilation was 21 +/- 19 h after amiodarone therapy versus 26 +/- 2 h in the control group (20 +/- 18 h vs. 15 +/- 9 h after excluding patients receiving OKT3), discharge arterial oxygen saturation was > 95% in both groups. Two patients in the amiodarone group with a smoking history of > 100 pack-years developed bilateral pulmonary infiltrates of brief duration. Although patients receiving amiodarone required atrial pacing more frequently (eight vs. two patients) and had a lower heart rate at discharge (75 +/- 18 vs. 86 +/- 11 beats/min), the duration of inotropic support (2.1 +/- 1.5 vs. 3.5 +/- 2.5 days) and of hospital stay (10 +/- 3 vs. 15 +/- 10 days) was not higher in the amiodarone than in the control group. The mortality rate at 30 days was similar in the two groups (6.8% vs. 3.4%, p = NS). CONCLUSIONS: Amiodarone therapy before heart transplantation may contribute to occasional pulmonary complications but does not significantly increase perioperative morbidity or mortality with the regimens used in this retrospective study.

Aged↗

PubMed1990

Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy.

To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation.

Adult↗