Tumor necrosis factor and cardiac function.

The direct effect of tumor necrosis factor (TNF), a product of activated macrophages, on myocardial performance was determined using an isolated papillary muscle technique and a modified Langendorff preparation. Papillary muscle was obtained from male adult rats 4-5 hours after they received either 100 ng/kg TNF (group A), or 100 micrograms/kg TNF (group B) or saline (control). Group B animals exhibited significantly greater peak tension development and velocity of contraction compared with controls (p less than 0.05). In group A animals these variables were not significantly different from those of the controls (p greater than 0.05). Electrophysiologic measurements revealed a significant decrease in resting membrane potential in both group A and group B animals compared with the controls (p less than 0.05). Whole hearts perfused with serum from animals treated with TNF 18-22 hours earlier exhibited significant impairment of contractility, decreased rate of systolic pressure development, and decreased rate of relaxation compared with the controls (p less than 0.05). Coronary flow and myocardial water content were similar for both groups of perfused hearts. These data suggest that tumor necrosis factor stimulates an early beneficial effect on myocardial function, which 18-22 hours later is associated with impairment of myocardial performance. This effect appears to be serum transferable.

Vascular reactivity following thermal injury.

Major thermal injury is associated with alterations in both pulmonary and systemic vascular resistance. Pulmonary artery hypertension may lead to right heart dysfunction and pulmonary insufficiency. The effect of thermal injury on vascular reactivity is unknown. Increases in circulating vasoactive substances, as well as alterations in vascular smooth muscle receptor activity, have been hypothesized to occur following thermal injury. We have studied aorta and pulmonary artery vascular sensitivity to five agonists in a 35% full-thickness thermal injury rat model. Vascular reactivity was normal to agonists that constrict vascular smooth muscle via receptor-mediated calcium influx. Unresuscitated and resuscitated burn injury resulted in a decrease in peak tension development to prostaglandin F2 alpha (PGF2 alpha) and potassium, agonists whose effects are mediated via membrane depolarization. Fluid resuscitation synchronous with burning did not alter peak tension development in agonists whose actions were mediated via receptor mechanisms. Peak tension development in resuscitated animals to agonists that affect contraction by depolarization remained deficient. To rule out simple blood loss as the etiology for these changes, the experiment was repeated in rats sustaining an acute 25% blood volume loss. Simple hypovolemia induced no changes in aortic or pulmonary vascular sensitivity. We hypothesize that thermal injury may result in a depolarization of vascular smooth muscle membranes altering voltage-dependent calcium channels.

Effects of fluid resuscitation on cardiac dysfunction following thermal injury.

To test the hypothesis that low cardiac output in burns is secondary to hypovolemia, the effects of resuscitation on isovolumic contracting rat heart following a full-thickness burn were studied. Sprague-Dawley rats were randomly assigned into three groups: (1) Sham burn, (2) 30% body surface area burn nonresuscitated, (3) 30% body surface area burn with 15 cc Ringer's lactate/180 g body wt ip at the time of burn resuscitated. Twenty hours postburn, the hearts were mounted on a Lagendorff perfusion apparatus. A balloon-tipped catheter placed in the left ventricle measured pressure and dp/dt. Coronary flow was determined. Myocardial samples for ATP and water were obtained. Left ventricular function was evaluated by recording peak systolic pressure, end diastolic pressure, and maximum +/- dp/dt while balloon volume was increased to 0.3 cc. Results are with end diastolic volume constant at 0.15 cc. Compared to sham burn, burn nonresuscitated generated lower peak systolic pressure +/- dp/dt and higher end diastolic pressure while hearts from burn resuscitated generated the same as sham burn. Coronary flow and tissue water content was similar in all. ATP content was lower in burn nonresuscitated. Our data support that impaired systolic and diastolic function in burn nonresuscitated hearts is associated with lower ATP levels not seen in burn resuscitated and reperfusion of burn nonresuscitated hearts does not reverse the myocardial depressant effect.

Renal vascular reactivity in jaundice.

Obstructive jaundice is associated with a predisposition to hypotension and acute renal failure that may be related to changes in renovascular responsiveness, particularly to norepinephrine (NE). This study was undertaken to investigate changes in vascular response to NE and to determine how these changes are related to prostaglandins. Kidneys from bile duct-ligated (BDL) rabbits (n = 5) were perfused with Krebs' solution at 7.65 ml/min, and the response to varying boluses of NE (0.78 to 6.24 micrograms) was measured as changes in perfusion pressure. When compared with sham-operated control kidneys (n = 8), a significantly blunted response was seen at all doses tested. The NE response was further assessed by measuring force development in mounted segments of main renal arteries (MRAs) (n = 8) and interlobar arteries (ILAs) (n = 6) from BDL rabbits and sham-operated controls (MRA, n = 8; ILA, n = 6). The dose-response curves were significantly depressed in both MRAs and ILAs from BDL animals. In addition, MRAs from sham-operated control animals exhibited decreased response to NE after incubation for 1 hour in jaundiced serum. This attenuated response of MRAs to NE was prevented when indomethacin (5 mg/kg) was given to BDL rabbits before death (n = 9) or when 10(-6)mol/L of indomethacin was added to jaundiced serum during incubation (n = 6). These results indicate that obstructive jaundice induces a decreased vascular contractile response in rabbits to NE and that this effect is mediated by prostaglandins.

The effects of burn injury and fluid resuscitation on cardiac function in vitro.

The effects of a 30% full-thickness total body surface area scald burn on in vitro mechanical cardiac function was studied in Sprague-Dawley rats. The findings were a 50% decrease in tension development and velocities of contraction and relaxation, when papillary muscle functions from sham and unresuscitated burned animals were compared. Fluid resuscitation synchronous with burning completely reversed the defects in papillary muscle function. This defect in function was partially transferable to normal muscles incubated in serum from burned rats.

In vitro reversal of cardiac deterioration in septic shock with tetraethylammonium chloride.

Overwhelming sepsis associated with cardiac failure continues to be a major clinical problem. This is commonly associated with a failure to respond to conventional pharmacologic therapy. This study was undertaken to see if manipulations of the electrophysiologic defects previously described by treatment with tetraethylammonium chloride (TEA) would be advantageous. Septic shock was induced in rabbits by a lethal dose of Escherichia coli. Peak tension and velocities of contraction and relaxation were measured in papillary muscle with and without 5mM TEA. Exposure to this compound improved peak tension and velocities of contraction and relaxation to normal values. The action of TEA is not specific to septic tissue as values in normal muscles are similarly improved. Tetraethylammonium chloride or other drugs that decrease outward potassium current and prolong the action potential duration may be helpful in treating cardiac dysfunction that accompanies sepsis.

Blood transfusions and survival after lung cancer resection.

The immunosuppressive effects of blood transfusions in renal transplantation patients are now well documented. The question arises as to whether the possible immunosuppressive effects of blood transfusions in cancer patients cause a more favorable host environment for tumor growth. One hundred fifty-five patients undergoing resection for lung carcinoma were analyzed retrospectively, and it was shown that the use of blood transfusions was associated with a significant decrease in survival time in patients undergoing curative resection of lung carcinoma despite multivariate adjustments for age, sex, cell type, right lung versus left lung location, type of operation, and stage. This association supports, but does not prove, the hypothesis that blood transfusions, possibly through an immunosuppressive mechanism, are responsible for a poorer prognosis in patients who undergo resection for carcinoma of the lung.

A physiologic explanation for cardiac deterioration in septic shock.

Utilizing analysis of multiple mechanical and electrophysiologic parameters, a technique for describing the myocardial depressant effects of septic shock was employed. Rabbit papillary muscle was exposed to septic shock serum obtained from dogs made hypotensive by infusing Escherichia coli 1-1.9 X 10(9) colony forming units per cubic centimeter (7 cc/kg). The exposure produced depression in action potential amplitude (47%), duration (32%), resting membrane potential (37%), velocities of phases 0 (31%), 2 (100%); phase 3 was preserved. Also, peak tension (62%) and velocity of contraction (51%) and relaxation (56%) were decreased. If the muscle was first exposed to 30 mM KCL solution, these depressions were eliminated. These data suggest the myocardial defects are mediated through abnormalities in fast channel activity.

Percutaneous needle biopsy of pulmonary lesions.

Percutaneous needle biopsy of lung lesions has proved useful in the diagnosis of tumors and infectious lesions of the lung. Accurate tissue diagnosis of tumors was obtained in 81 percent of attempts, and an accurate microbiologic diagnosis was obtained in 75 percent of infectious lesions. Eleven percent (23 of 213) of patients biopsied for tumor were spared diagnostic thoracotomy, and only one biopsy gave a false-positive result. There has been no mortality, and the only significant morbidity was a 12 percent incidence of pneumothorax necessitating chest tube insertion. The use of this technique in varied clinical settings has made it a valuable and often primary diagnostic tool for lung lesions.

Achalasia and diffuse oesophageal spasm in siblings.

We report the occurrence of achalasia and diffuse oesophageal spasm in brother and sister. The familial occurrence of these unusual disorders is consistent with the possibility that they share a common aetiology and indicates the potential importance of genetic predisposition.

Adult respiratory distress syndrome (ARDS), sepsis, and extracorporeal membrane oxygenation (ECMO).

This report presents data obtained in the care of 830 patients requiring assisted ventilation. When these patients were divided into groups by the severity of their respiratory failure as defined by the duration of ventilatory assistance (greater than 48 hours, less than 48 hours) and level of positive end expiratory pressure (PEEP) required (greater than 5 cm HoH, less than 5 cm HoH), it was found that evidence of concurrent bacterial infection was present in the majority of patients with severe respiratory failure. This finding could not be explained by infection acquired after the onset of respiratory failure. In addition, this analysis demonstrated the important association of active pulmonary infection with the occurrence of barotrauma in these patients. Case analysis of patients subjected to extracorporeal membrane oxygenation has led to the suggestion that underlying sepsis in patients failing to respond to conventional ventilatory assistance similarly limits the usefulness of membrane oxygenator support.

Removal of intraaortic balloon without vascular complications.

A technique for inserting and removing the intraaortic balloon pump without vascular complications is descirbed. Prevention of clot formation at the graft-arterial junction, preservation of collateral circulation by insertion in the common femoral artery, removal of potentially infected graft material, and enlargement of the common femoral artery by patch angioplasty are important factors.

Esophageal perforation following use of esophageal airway.

The esophageal airway has gained increasing acceptance in airway management during cardiopulmonary resuscitation, and its enthusiastic advocates are urging expansion of its use. A fatal case of esophageal perforation following the use of an esophageal airway is presented. Possible contributing factors are discussed. A modified esophageal airway which seems safer and more versatile, effective, and economic is described.

A technique for direct measurement of left atrial pressure after cardiac operations.

A grooved director bent to a "hockey stick" configuration serves as an effective catheter guide to assure accurate placement of a left atrial pressure measuring catheter.

Ineffectiveness of methylprednisolone in the treatment of pulmonary dysfunction after cardiopulmonary bypass.

Fifty consecutive adults undergoing elective cardiac surgery with cardiopulmonary bypass received a single dose of methylprednisolone (30 mg/kg) at the time of anesthesia. The results were compared with those in the immediately preceding fifty adult patients who underwent elective cardiac surgery and who did not receive corticosteroids. The age, sex, and weight of the patient, mortality, nature of the lesions treated surgically, bypass time, smoking history, physiologic evidence of preexisting lung disease, preoperative New York Heart Association class, preoperative left ventricular end diastolic pressure, incidence and duration of the postoperative low cardiac output syndrome, postoperative arrhythmias, operative and postoperative blood loss and postoperative hours of respiratory support, dynamic lung-thorax compliance, alveolar arterial oxygen gradient, fraction of wasted ventilation, and incidence of tracheostomy were tabulated and statistically contrasted. The two groups were comparable relative to all preoperative factors, except for a slightly higher end diastolic pressure in the patients who received steroids. Methylprednisolone given at the time of anesthesia was associated with a higher intraoperative blood loss, a higher incidence of low cardiac output syndrome, and an increased requirement for postoperative mechanical ventilation. As bypass time approached three hours, the proportion of patients requiring prolonged support in both groups became similar. It was concluded that pretreatment with methylprednisolone in massive doses had an overall adverse cardiopulmonary effect.