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Burn treatment requires large volumes of crystalloid, which may exacerbate burn-induced cardiopulmonary dysfunction. Small-volume hypertonic saline dextran (HSD) resuscitation has been used for effective treatment of several types of shock. In this study isolated coronary perfused guinea pig hearts were used to determine if HSD improved left ventricular contractile response to burn injuries. Parameters measured included left ventricular pressure (LVP) and maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max) at a constant preload. Third-degree scald burns comprising 45% of total body surface area (burn groups, N = 75), or 0% for controls (group 1, N = 25) were produced using a template device. In group 2, 25 burned guinea pigs were not fluid resuscitated and served as untreated burns; 20 burns were resuscitated with 4 mL lactated Ringer's (LR) solution/kg/% burn for 24 hours (group 3); additional burn groups were treated with an initial bolus of HSD (4 mL/kg, 2400 mOsm, sodium chloride, 6% dextran 70) followed by either 1, 2, or 4 mL LR/kg/% burn over 24 hours (groups 4, 5, and 6, respectively). Untreated burn injury significantly impaired cardiac function, as indicated by a fall in LVP (from 88 +/- 3 to 68 +/- 4 mmHg; p = 0.01) and +/- dP/dt max (from 1352 +/- 50 to 1261 +/- 90 and from 1150 +/- 35 to 993 +/- 59; p = 0.01, respectively) and a downward shift of LV function curves from those obtained from control hearts. Compared to untreated burns, hearts from burned animals treated with LR alone showed no significant improvement in cardiac function. However hearts from burned animals treated with HSD + 1 mL LR/kg/% burn had significantly higher LVP (79 +/- 4 vs. 68 +/- 4 mmHg, p = 0.01) and +/- dP/dt max (+dP/dt: 1387 +/- 60 vs. 1261 +/- 90 mmHg/sc, p = 0.01; -dP/dt: 1079 +/- 50 vs. 993 +/- 59 mmHg/sc, p = 0.01) than hearts from untreated burned animals and generated left ventricular function curves comparable to those calculated for hearts from control animals. Mortality 24 hours after burn was 29% for untreated burns was 0% for control animals, as well as for groups treated with the Parkland formula or HSD plus 1 or 2 mL/kg/% burn lactated Ringer's. The only deaths after treatment occurred in those animals given HSD plus 4 mL/kg/% burn, Parkland formula (17% mortality).(ABSTRACT TRUNCATED AT 400 WORDS)

Atrial muscle isolated from burned guinea pigs was used to assess myocardial contractile changes associated with thermal injury. Muscle was obtained 16-18 hours after the animals were subjected to sham burn (controls) or to scald burn equivalent to 16% of total body surface area. Isometric contractile tension (CT) and its maximal rate of increase (+dT/dt) were not significantly altered by burn. However, the maximal rate of relaxation (-dT/dt) was uniformly less in muscle from the burned group, and this difference was significant at several time intervals after in vitro contractile responses were elicited. Similarly, -dT/dt responses to increased stimulation frequency (0.1-3.0 Hz) and to increased calcium ion concentration (1.0-10.0 mM) were generally less in the burned group, whereas corresponding CT and +dT/dt responses of the burn and controls groups were not significantly different. Present data indicate that atrial muscle removed from moderately burned guinea pigs exhibits normal contractile capabilities, but may be characterized by impaired relaxation properties.

Conscious guinea pigs were used to study the development of burn shock as a function of the size of thermal injury to the body surface. Scale burns equivalent to 0 (control, n = 18), 15.7 +/- 0.8% (n = 11), 24.6 +/- 0.5% (n = 10), and 43.4 +/- 1.5% (n = 10) of total body surface area were obtained by use of a template device, while the animals were deeply anesthetized with methoxyflurane. Circulatory function was assessed without further anesthetic restraint before and at 1, 2, 4, 6, 8, and 24 hr after burn. Values from control guinea pigs varied little during the observation period. Hemodynamic functions of burned guinea pigs were abnormal, and both the magnitude and duration of dysfunction generally depended upon the size of injury. Burn shock was characterized by hemo-concentration, hypothermia, tachycardia (bradycardia in the 43.4% group), minimal adjustments in systemic blood pressure, hyperkalemia, normonatremia (hyponatremia in the 43.4% group) arterial acidemia, and decreased respiratory rate. Circulatory functions of the 15.7% and 24.6% groups returned toward control levels during 8 hr after burn. Severe shock persisted in the 43.4% group, which experienced 70% mortality by 24 hr. These experiments characterize the guinea pig as a reproducible small animal model for studying different severities of burn shock unencumbered by secondary influences associated with general anesthesia.

The release of oxygen free radicals from ischemic myocardium has been implicated as a causative factor of cardiac dysfunction after thermal injury. In this study, isolated coronary perfused guinea pig hearts were used to determine if free radical scavengers improve left ventricular (LV) intrinsic contractile response to burn shock. Parameters measured included peak isovolumic LV pressure (LVP) and maximal rate of LVP rise (+dP/dtmax) and fall (-dP/dtmax) at a constant preload. Control animals were immersed in body temperature water and divided into four groups: Group 1, untreated N = 10; Group 2, control animals treated with unbound superoxide dismutase (SOD), N = 5; Group 3, control animals treated with ficoll-SOD, N = 5; and Group 4, control animals treated with PEG-SOD, N = 5. Scald burn equivalent to 45% of total body surface area was produced in 64 animals. Fluid resuscitation was initiated immediately after burn in all animals, and animals were then divided into seven burn experimental groups. In Group 5, 10 animals were treated with fluid alone, lactated Ringer's, 4 mL/kg/% burn. Burned animals in Group 6 (N = 10) received a reduced volume of Ringer's 2 mL/kg/% burn plus unbound-SOD, 50 mg/kg; 10 animals in Group 7 received this volume of Ringer's plus ficoll-SOD, 50 mg/kg. In groups 8, 9, and 10 animals were given fluid, lactated Ringer's, 2 mL/kg/% burn plus varying doses of PEG-SOD (Group 8: N = 9, 1,000 U; Group 9: N = 10, 6,000 U; Group 10: N = 5, 12,000 U). In Group 11 (N = 10), animals received SOD-PEG, 6,000 U, plus catalase, CAT-PEG, 6,000 U, given with 4 mL/kg/% burn lactated Ringer's solution. Hypotension, hypothermia, and hemoconcentration were similar in all animals after thermal injury, regardless of treatment regimen. Burn hearts showed significantly lower LVP, +dP/dt max, and -dP/dt max than control hearts (P less than 0.05). Compared to controls, coronary pressure and coronary vascular resistance were significantly higher in all treated burn groups. There was no significant difference in heart rate or time to peak pressure or time to maximal contraction or relaxation among the groups. Left ventricular function curves for burned hearts were shifted downward and to the right of curves obtained from control hearts (P less than 0.01), regardless of scavenger treatment. PEG-SOD, 6,000 U, improved left ventricular contractility (+dP/dt) at maximal levels of end-diastolic pressure but deficits in left ventricular pressure and relaxation persisted.(ABSTRACT TRUNCATED AT 400 WORDS)

Isolated coronary perfused hearts from guinea pigs were used to determine if aging alters left ventricular (LV) intrinsic contractile response to resuscitated burn shock. Parameters measured included LV pressure (LVP) and maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max) at a constant preload (LV enddiastolic pressure [LVEDP]). Compared with young controls (ten), aged control hearts (ten) showed significantly lower LVP (87.4 +/- 2.53 versus 76.0 +/- 1.5, p,0.001), +dP/dt max (1,351 +/- 51 versus 1,048 +/- 49, p,0.001), and -dP/dt max (1,154 +/- 34 versus 916 +/- 27, p,0.001), at an LVEDP of 10 millimeters of mercury. A 43 +/- 2 per cent third-degree burn (Walker model) was studied in ten young and ten aged guinea pigs. Burned aged hearts showed significantly lower LVP (57.1 +/- 2.1 versus 67.5 +/- 3.7, p,0.01) and -dP/dt max (707 +/- 33 versus 993 +/- 59, p,0.001) at an LVEDP of 10 millimeters of mercury. In addition, LV function curves for burned aged hearts were shifted downward and to the right of curves obtained from young burned hearts (p,0.05). Contractile defects in the aged group were not overcome by altered beating frequency, increased extracellular calcium concentration, nor maximally effective increases in diastolic stretch. Finally, we examined the effects of fluid resuscitation (4 milliliters per kilogram per percentage of burns) on contractile function in an additional ten young and ten aged burned guinea pigs. Contractile deficits persisted in both age groups despite adequate fluid resuscitation. Peak LVP and maximal rate of relaxation (-dP/dt) were uniformly depressed in aged as compared with young burned hearts (52.4 +/- 1.5 versus 63.2 +/- 2.7 and 715 +/- 42 versus 909 +/- 52, p,0.01, respectively). These data suggest that severe myocardial contractile change resulting from a major thermal insult in subjects with already compromised hearts is likely a significant limiting factor in the response to burn shock and adequate fluid resuscitation.

Isolated coronary perfused guinea pig hearts were used to determine if aging alters left ventricular (LV) intrinsic contractile response to unresuscitated burn shock. We first compared control hearts from both young (N = 10) and aged (N = 10) guinea pigs. Compared with young control hearts, aged control hearts showed significantly lower left ventricular performance (LVP) (84.2 +/- 1.6 v 76.0 +/- 1.5; P less than 0.003), +dP/dtmax (1417.5 +/- 52.4 v 1048 +/- 48.7; P less than 0.001), and -dP/dtmax (1079 +/- 79 v 916 +/- 27; P less than 0.001) at a left ventricular end-diastolic pressure (LVEDP) of 10 mmHg. A 43% +/- 2% third-degree burn (Walker model) was studied in 20 young and 10 aged guinea pigs. The aged burn hearts showed significantly lower LVP (57.1 +/- 2.1 v 65.5 +/- 2.0; P less than 0.01) and +dP/dtmax (1026 +/- 66.4 v 1219 +/- 59.9; P less than 0.001) at an LVEDP of 10 mm Hg. In addition, LV function curves for the aged burn hearts were shifted downward and to the right of curves obtained from the young burn hearts (P less than 0.05). Contractile defects in the aged group were neither related to altered beating frequency nor to maximally effective increases in diastolic stretch. While increased extracellular calcium concentration (from 1 to 8 millimolar [mM]) increased LVP, +dP/dtmax, and -dP/dtmax in a dose-dependent manner in both young and aged burn hearts, absolute values of measured contractile performance were consistently less in the aged hearts compared with the young hearts at identical calcium concentrations. Finally, we examined the effects of thermal injury on contractile function within the aged group. Peak LVP and maximal rate of relaxation were uniformly decreased in all burn hearts compared with control aged hearts. The +dP/dtmax was not significantly altered by burn in this age group (burn: 1026 +/- 66; control: 1048 +/- 49). This study suggests that severe myocardial contractile changes resulting from a major thermal insult in subjects with already compromised hearts is likely a significant limiting factor in the response to burn shock.