Resolution of experimental pneumothorax in rabbits by oxygen therapy.

The treatment of asymptomatic patients with small pneumothoraces (ie, less than 20% by volume) has included observation, tube thoracostomy, and operation. When observation is used, the anticipated expansion of the lung has been estimated to be 1.25% of the lung volume daily. This study was designed to evaluate the use of inhaled oxygen as a method to accelerate the resolution of a pneumothorax in a rabbit model. Experimental pneumothoraces were created in 23 white New Zealand rabbits. Group 1 (9 rabbits) were placed in a cage with room air and group 2 (11 rabbits) were placed in a cage with high oxygen concentration. Three rabbits died before completion of the study. Serial chest roentgenograms were performed until the pneumothoraces resolved. The majority of rabbits treated with oxygen had resolution of their pneumothoraces by 36 hours, whereas the majority of rabbits treated with room air did not show complete resolution before 48 hours. Biopsies showed no evidence of damage secondary to oxygen treatment. Oxygen treatment was found to be significantly better in the early resolution of pneumothoraces when compared with room air. This establishes an alternative treatment for some pneumothoraces that are small and asymptomatic.

Preservation of adenosine 5'-triphosphate and mitochondrial function during hypercalcemic reperfusion using verapamil cardioplegia.

Immediate hypercalcemic reperfusion results in ventricular dysfunction and loss of high-energy stores. The purpose of this study was to evaluate the effect of verapamil cardioplegia on the preservation of myocardial energy stores, mitochondrial ultrastructure, and ventricular dysfunction in the postischemic rat heart during immediate hypercalcemic reperfusion. Rats in the control group were subjected to cardioplegia with potassium, while rats in groups 1 to 3 were subjected to the same with verapamil (0.5 mg/L). The control and group 1 rats underwent normocalcemic reperfusion and groups 2 and 3 rats underwent hypercalcemic reperfusion. Myocardial samples were analyzed for adenosine 5'-triphosphate (ATP) content and mitochondrial ultrastructural damage. Hemodynamic parameters of heart rate, aortic flow (AF), and postischemic rate of aortic pressure change (dP/dT) also were evaluated. Data were analyzed using analysis of variance. The ATP stores were preserved at greater than 100% control levels in hearts subjected to verapamil cardioplegia. There was no evidence of irreversible mitochondrial damage. Heart rate, AF, and dP/dT were significantly (p < 0.05) depressed in hearts subjected to verapamil cardioplegia. This study suggests verapamil cardioplegia preserves ATP and mitochondrial function during immediate hypercalcemic reperfusion but does not improve postischemic hemodynamics.

Myocardial performance after contusion with concurrent hypovolemia.

Myocardial contusion may present as a benign nonclinical event or a life-threatening emergency. Although cardiac output is recognized to be decreased with major contusion, the contribution of hypovolemic shock to myocardial dysfunction is unclear. This study was designed to evaluate the relationship between myocardial contusion and hypovolemic shock. After Sprague-Dawley rats were anesthetized, contusions were administered at either 80 psi or 120 psi. Half of each group then underwent hypovolemic shock. After 24 hours of recovery, cardiac hemodynamics were studied in each subgroup using the Neely-Langendorff apparatus. Isoenzymes and histology were evaluated as well. The data showed that rats undergoing hypovolemic shock in each subgroup had a significant decrease in cardiac output when compared with their controls. This decrease was more pronounced in the 120-psi group. Cardiac isoenzyme levels were elevated in all groups. Microscopic evaluations showed contusion in the controls and necrosis in the shock groups. Patients whose injuries are compatible with myocardial contusion and hypovolemic shock should be resuscitated quickly and evaluated for myocardial dysfunction secondary to infarction.

Delta and Mu receptor agonists correlate with greater depression of cardiac function than morphine sulfate in perfused rat hearts.

In previous studies done in our laboratory, we demonstrated that morphine sulfate could depress heart rate and cardiac output when added to the perfusate of a working rat heart model using a modified Langendorff preparation. In this study we investigated three different delta agonists and a mu agonist by adding each to the perfusate in a fashion similar to the experiments done with morphine sulfate. We found that all three delta agonists, leu-enkephalin, D-ala-D-leu-enkephalin (DADL), and D-Pen enkephalin, would significantly decrease cardiac output. In the case of D-Pen enkephalin, heart rate and stroke volume were also significantly decreased. Additionally the mu agonist Tyr-D-ala-gly-N-met-phe-gly-ol (DAGO) also caused a significant decrease in heart rate, cardiac output, and stroke volume. The data suggest that all three delta agonists and DAGO are capable of depressing heart rate, cardiac output, and stroke volume at concentrations between 10(3) and 10(4) lower than those used in studies with morphine sulfate.

Correlation of plasma beta-endorphin levels with mean arterial pressure and cardiac output in hypovolemic shock.

Recent studies have been conducted to evaluate the relationship between plasma beta-endorphin (END) levels and the hemodynamic changes that occur in severely stressed animals. Using our canine hypovolemic shock model, END levels were analyzed during the baseline period, at the beginning of treatment (after a period of fixed-pressure hypovolemic shock), and at the end of treatment. Mean arterial pressure (MAP) and cardiac output were also measured at these intervals. Animals were given iv 5 ml of 0.9% NaCl, 4 mg/kg of naloxone (NAL), 30 mg/kg of methylprednisolone (MP), or 4 mg/kg of NAL and 30 mg/kg of MP. A fifth group was composed of nonsteroid-treated animals. Scatterplots were generated and linear regression lines were drawn comparing END with cardiac output and MAP. In the nonsteroid-treated animals, a significant correlation was found between decreases in both MAP and cardiac output and increasing levels of END. The addition of MP did not seem to alter the relationship, suggesting that MP did not affect END release.

Myocardial opiate receptor activity is stereospecific, independent of muscarinic receptor antagonism, and may play a role in depressing cardiac function.

Earlier work has shown that morphine sulfate can produce a dose-related decrease in heart rate (HR) and cardiac output (CO) in isolated working rat hearts. This response is preventable with the use of the opiate receptor antagonist, naloxone hydrochloride. In this study, the stereospecificity of the opiate response was tested with the use of levorphanol tartrate and its d-isomer, dextrorphan, in our Langendorff rat heart model. The interaction of muscarinic receptor activity with the opiate response was tested by first adding bethanechol chloride to the perfusate in the presence and absence of atropine (5 X 10(-9) mmol/L). Our earlier studies with morphine sulfate were then repeated in the presence of the same concentration of atropine. At a concentration of 5 X 10(-6) mmol/L, levorphanol tartrate produced a significant decrease in CO (p less than 0.05), while a similar concentration of dextrorphan produced little change in either HR or CO. Bethanechol chloride, in a concentration of 3 X 10(-6) mmol/L, produced a significant decrease in HR and CO (p less than 0.05), which was prevented by atropine. When morphine sulfate was added to the standard perfusate (3 X 10(-4) mmol/L), HR and CO were significantly decreased (p less than 0.05). This change was not prevented by the addition of atropine. The opiate effect on myocardial function is mediated by a stereospecific opiate receptor, which acts independently of muscarinic receptor antagonism.

Hemodynamic evaluation of ibuprofen in canine hypovolemic shock.

This study was done to evaluate the role of ibuprofen, a cyclooxygenase inhibitor, in a standard model of hypovolemic shock. Fifteen dogs were subjected to fixed mean arterial blood pressure (MABP) shock (40-45 mmHg) for 45 min and then treated with physiologic saline (NS), low-dose ibuprofen (6.25 mg/kg), and high-dose ibuprofen (12.5 mg/kg) by IV bolus and continuous IV infusion. After 60 min of treatment, the shed blood was returned. Survival was monitored for 72 h. Both dose levels resulted in a significant increase in MABP and total peripheral resistance over NS during the infusion period but heart rate, cardiac output, and left ventricular contractility were similar for all groups. Survival at 72 h was also similar for the three groups. Ibuprofen treatment, while increasing MABP and total peripheral vascular resistance did not seem to alter cardiac function or improve survival when compared to NS in this model of hypovolemic shock.

Morphine sulfate depression of cardiac function is attenuated by opiate receptor antagonism with naloxone.

In previous work, morphine sulfate was shown to decrease heart rate (HR) and cardiac output (CO) in a dose-related fashion. It was hypothesized that this effect was mediated by opiate receptors located in the myocardium. The present study evaluated the effect of opiate receptor antagonism with naloxone using a modified Langendorff rat heart perfusion apparatus. Sixty-five rat hearts were excised and perfused with Krebs-Henseleit buffer (KHB) solution, to which morphine sulfate and naloxone (NAL) were added in different concentrations. In the initial studies, NAL (10(-5) M) was added to the perfusate prior to the incremental additions of morphine. This resulted in no antagonism of the previously described opiate agonist effects. Norepinephrine (NE; 10(-9) M) was then added to the perfusate prior to the NAL or morphine. The NE did not affect the dose-related decrease in HR and CO when morphine was added but did permit the attenuation of the morphine effect by the addition of increasing concentrations of NAL up to 10(-5) M. These results suggest that the agonist effect can be attenuated by opiate receptor antagonism with NAL; the data also suggest a possible interrelationship between opiate and catecholamine receptor activity in the myocardium.

Beneficial effect of thyrotropin-releasing hormone in canine hemorrhagic shock.

The effects of thyrotropin-releasing hormone (TRH) on hemodynamic variables, oxygen delivery (DO2), and oxygen consumption (VO2) variables in canine hemorrhagic shock were studied. Anesthetized adult dogs were bled over 30 min to a mean arterial pressure (MAP) of 50 mm Hg. Shock was maintained at this level for half an hour. The animals were divided alternatively into two groups. In the first group (n = 5) a bolus of TRH (2 mg/kg) was given intravenously. The second group (n = 5) served as control and received equal amounts of D5W. Blood samples were obtained regularly up to 120 minutes after TRH or placebo. Differences in the two groups were statistically tested. After TRH, MAP pressure, cardiac output, and systemic vascular resistance increased significantly. DO2 improved after TRH but VO2 remained unchanged. In all dogs, sequential beta endorphin level were measured and were shown to rise after induction of shock. This data indicates that TRH may be of therapeutic benefit in the treatment of hemorrhagic shock and that beta endorphin may be an important pathophysiologic factor.

Effect of methylprednisolone on naloxone's hemodynamic response in canine hypovolemic shock.

Previous studies have suggested that methylprednisolone (MP) pretreatment attenuates the usual hemodynamic response to naloxone (NAL) treatment of hypovolemic shock. In this study, both drugs were given concurrently during shock to evaluate hemodynamic changes, plasma endorphin-like activity (PELA), and survival. Twenty-six dogs were bled to a mean arterial pressure (MAP) of 40 to 45 mm Hg, which was maintained for 45 min. Animals were then treated with iv 0.9% NaCl (NS), 5 ml; NAL, 4 mg/kg; MP, 30 mg/kg; or NAL, 4 mg/kg, plus MP, 30 mg/kg. Animals treated with NAL and/or MP had significantly (p less than .05) improved MAP, cardiac output, and myocardial contractility compared with NS-treated animals. NAL and MP each significantly lowered PELA levels and both NAL and NAL plus MP significantly improved survival.

Late administration of methylprednisolone does not enhance naloxone effect in hypovolemic shock.

The late addition of methylprednisolone (MP) in our canine hypovolemic shock protocol was evaluated to determine whether any hemodynamic enhancement of the naloxone (NAL) effect might be present. Thirty-four dogs were bled to a mean arterial pressure (MAP) of 40-45 mm Hg and held there for 45 minutes. All animals were then treated (T = 0) with 0.9% NaCl (NS) or NAL. In two groups of animals, MP (30 mg/kg) was given as an IV bolus 30 minutes after initiating NS or NAL therapy. At 60 minutes, the infusions were stopped and the shed blood was returned. Animals treated with NAL with or without MP showed improvement in MAP, maximal left ventricular contractility (LVdP/dt max), and cardiac output (CO) compared to NS. We found little hemodynamic improvement with the addition of MP at T = 30 for either the NAL or NS. Plasma endorphinlike activity (PELA) values decreased during treatment in the groups receiving NAL. Survival was improved in all groups except those receiving NS, but survival was statistically better only in the group that received NAL.

The effect of retinol and retinoic acid on physiological and biochemical changes in retinol-deficient rats.

1. The effects of retinol and retinoic acid supplementation of retinol-deficient rats were studied for a variety of metabolic processes shown to be affected by retinol-deficiency. 2. Retinol-deficient rats were found to have decreased body-weight, liver and testes weights, a degeneration of testicular germinal cells, an increased incorporation of labelled choline into liver and testes phospholipids, an increased protein synthetic activity (in vitro) of liver ribosomes, an increased transfer-RNA methyltransferase activity in liver and a decreased activity in testes, an increased DNA content of testicular nuclei, and a decreased uptake of [3-H]thymidine by testicular nuclear DNA. 3. In retinol-deficient rats supplemented for 8 weeks with retinol these changes were reversed, measurements returning to control levels. 4. In retinol-deficient rats supplemented for 8 weeks with retinoic acid all changes were reversed except those in the testes. 5. Testicular signs of retinol deficiency appeared to be delayed when retinoic acid was added to the retinol-deficient diet of weanling rats. This suggests a sparing action of retinoic acid on the rat's utilization of retinol. 6. Suggestions are offered as to why retinoic acid will support growth and development but not spermatogenesis in the rat.