Abstract | OBJECTIVE: To examine the effects of pharmacologic agents designed to limit burn-mediated calcium overload on cardiomyocyte [Ca2+] and cardiac contractile function. DESIGN: Experimental, comparative study. SETTING: Cellular biology and physiology laboratory. SUBJECTS: Adult Sprague Dawley rats. INTERVENTIONS: Rats were given third-degree burn injury over 40% of the total body surface area, were fluid resuscitated, and then were divided randomly to receive one of five treatments: vehicle ( normal saline); amiloride (50 mg/kg) to inhibit H+-Na+ exchange and subsequent Na+-Ca2+ exchange; dantrolene (10 mg/kg, 30 mins, 6 and 22 hrs postburn) to inhibit sarcoplasmic reticulum Ca2+ release; diltiazem (10 mg/kg given over first 6 hrs postburn); or amlodipine (0.07 mg/kg, 24 hrs preburn and 30 mins postburn) to block calcium slow channels. Appropriate controls ( sham burns given the appropriate pharmacologic agent) were included in each group. Twenty-four hrs postburn, left ventricular function (Langendorff), cardiomyocyte [Ca2+]i and [Na+]i measured by fura-2-AM or sodium-binding benzofurzan isophthalate loading of cardiomyocytes, and myocyte secretion of tumor necrosis factor-alpha ( enzyme-linked immunosorbent assay) were assessed in shams and burns from each experimental group. This time point was selected based on our previous work confirming maximal ventricular contractile defects and maximal cytokine secretion 24 hrs postburn. MEASUREMENTS AND MAIN RESULTS: CONCLUSION: Our data suggest that the calcium antagonists used in this study provide cardioprotection by modulating several aspects of the overall inflammatory cascade rather than solely limiting cardiomyocyte accumulation of calcium.
|
Authors | D Jean White, David L Maass, Billy Sanders, Jureta W Horton |
Journal | Critical care medicine
(Crit Care Med)
Vol. 30
Issue 1
Pg. 14-22
(Jan 2002)
ISSN: 0090-3493 [Print] United States |
PMID | 11902254
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Calcium Channel Blockers
- Tumor Necrosis Factor-alpha
- Amlodipine
- Amiloride
- Sodium
- Diltiazem
- Dantrolene
- Calcium
|
Topics |
- Amiloride
(pharmacology, therapeutic use)
- Amlodipine
(pharmacology, therapeutic use)
- Animals
- Burns
(drug therapy, metabolism)
- Calcium
(metabolism)
- Calcium Channel Blockers
(pharmacology, therapeutic use)
- Dantrolene
(pharmacology, therapeutic use)
- Diltiazem
(pharmacology, therapeutic use)
- Myocardial Contraction
(drug effects, physiology)
- Myocardium
(metabolism)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Sodium
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
- Ventricular Function, Left
(drug effects, physiology)
|