J. R. Michael

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs.

The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of epinephrine on cerebral and myocardial perfusion in an infant animal preparation of cardiopulmonary resuscitation.

We assessed the efficacy of conventional cardiopulmonary resuscitation (CPR) in 2-week-old piglets. We determined intrathoracic vascular pressures, cerebral (CBF) and myocardial blood flows (MBF), and cerebral oxygen uptake during conventional CPR in this infant animal preparation and contrasted these results with those of previous work on adult animals. We further examined the effects of the infusion of epinephrine on these pressures and flows and on cerebral oxygen uptake, which has not been previously evaluated in adult preparations. Conventional CPR was performed on pentobarbital-anesthetized piglets with a 20% sternal displacement with the use of a pneumatic piston compressor. Chest recoil was incomplete, leading to an 18% to 27% reduction in anteroposterior diameter during the relaxation phase. Aortic and right atrial pressures in excess of 80 mm Hg were generated. These pressures are greater than those generally obtained in adult animals with similar percent pulsatile displacements. CBF and MBF were also initially greater than those reported in adult animals undergoing conventional CPR. However, when CPR was prolonged beyond 20 min, aortic pressure fell and CBF and MBF declined to the near-zero levels seen in adult preparations. At 5 min of CPR, CBF and MBF were 24 +/- 7 and 27 +/- 7 ml . min-1 x 100 g-1 (50% and 17% of the values during cardiac arrest), respectively. With the continuous infusion of epinephrine (4 micrograms/kg/min) in another group of animals, MBF was significantly greater at 20 min of CPR and CBF and cerebral O2 uptake were greater at 35 min of CPR as a result of higher perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effect of epinephrine infusion on cerebral and myocardial blood flows during CPR

It is hypothesized that epinephrine improves the ability to resuscitate the heart through a mechanism thought to be related to the increase in aortic pressure. Our results with epinephrine infusion during CPR are consistent with this hypothesis. Epinephrine selectively increased vascular resistance in noncerebral, noncoronary vascular beds, as indicated by a decrease in microsphere-determined blood flow in these areas. This increased vascular resistance raised aortic pressure during the chest compression phase and the relaxation phase of CPR. Because intracranial and right atrial pressures were only slightly higher with epinephrine, cerebral and myocardial perfusion pressures and blood flows were significantly improved. This beneficial effect (compared to no administration of a vasopressor) was more pronounced as CPR progressed beyond ten minutes. Enhanced cerebral and myocardial perfusion occurred with epinephrine when either the conventional or simultaneous compression and ventilation (SCV) mode of CPR was employed in dogs. Similar selective perfusion was sustained for 50 minutes of SCV-CPR with epinephrine, even when the onset of CPR was delayed five minutes. Regional brain blood flow differed in the delayed-CPR group in that cerebellum, brain stem, and thalamic regions initially had higher blood flows. In an infant animal model of CPR using conventional CPR in piglets, epinephrine also was found to increase cerebral and myocardial blood flows. These results show that administration of epinephrine benefits different age groups of different species with different modes of CPR; that benefits occur even with delayed onset of CPR which is associated with additional anoxia and acidosis; and that epinephrine administration is particularly effective in sustaining cerebral and coronary perfusion during prolonged CPR.

Blood Flow during Cardiopulmonary Resuscitation with Simultaneous Compression and Ventilation in Infant Pigs

ABSTRACT: We determined whether the simultaneous chest compression and ventilation (SCV) technique of cardiopulmonary resuscitation (CPR) enhances cerebral (CBF) and myocardial (MBF) blood flows and cerebral O2 uptake in an infant swine model of CPR as it does in most adult animal CPR models. We also tested whether SCVCPR sustains CBF and MBF for prolonged periods of CPR when these flows ordinarily deteriorate. CPR was performed in two groups (n=8) of pentobarbital anesthetized piglets (3.5-5.5 kg) with continuous epinephrine infusion (10µg/kg/min). Conventional CPR was performed at 100 compressions/min, 60% duty cycle, 1:5 breath to compression ratio and 25-30 mm Hg peak airway pressure. SCVCPR was performed at 60 compressions/min, 60% duty cycle and 60 mm Hg peak airway pressure applied during each chest compression. Peak right atrial and aortic pressures in excess of 80 mm Hg were generated during CPR in both groups. At 5 min of conventional and SCV-CPR, MBF was 38 ± 7 and 46 ± 7 mL· min-1· l00 g-1 (±SE), respectively, and CBF was 15 ± 3 and 13 ± 2 mL· min-1· 100 g-1respectively. However, as CPR was prolonged to 50 min, the sternum progressively lost its recoil and the chest became more deformed. Lung inflation at high airway pressure with SCV-CPR did not prevent this chest deformation. Aortic pressure gradually declined, whereas right atrial and intracranial pressure remained constant in both groups. Consequently, MBF and CBF fell less than 10 mL· min-1· 100 g-1 and cerebral O2 uptake was markedly impaired during prolonged conventional and SCV-CPR. Therefore, SCV-CPR in an infant swine model does not enhance MBF and CBF during early CPR because intrathoracic pressure generation is already high with conventional CPR as reflected by the high right atrial pressure. In addition, SCV-CPR does not prevent the progressive chest deformation and the subsequent decline in CBF and MBF when CPR is prolonged, as is often required in pediatric resuscitation.

Community-acquired acinetobacter pneumonia

Acinetobacter calcoaceticus var anitratus, a nonfermentative grampnegative bacillus, has been infrequently reported as a cause of community-acquired pneumonia. In this paper we describe the course of six recent patients with community-acquired, bacteremic pneumonia due to this organism and review the six previously reported cases. Our experience suggests this organism is a more common cause of community-acquired pneumonia than previously thought. Acinetobacter pneumonia occurs in older persons with chronic disease, especially alcoholism. It is a fulminant illness with respiratory distress, hypoxemia, leukopenia and shock. Chest roentgenograms reveal a lobar or bronchopneumonic infiltrate which often becomes bilateral within 24 hours of admission to the hospital. Pleural effusions are common. The mortality rate is 43 per cent. Factors that predict a fatal outcome are granulocytopenia, empyema and therapy with inappropriate antibiotics. Therapy with appropriate antibiotics, especially carbenicillin and an aminoglycoside, increases survival.

Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine.

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.

Acute Pulmonary Disease Caused by Phenytoin

Acute pulmonary disease may occur as part of the hypersensitivity angitis produced by phenytoin sodium. The clinical features of the pulmonary involvement are fever, dyspnea, hypoxemia, and bilateral radiographic infiltrates. The pathologic process is an interstitial pneumonitis that appears reversible with cessation of the drug and treatment with corticosteroids.

Calcium channel blockers in hypoxic pulmonary hypertension

Hypoxia is the major cause of pulmonary hypertension and right ventricular hypertrophy in chronic obstructive pulmonary disease, cystic fibrosis, kyphoscoliosis, chronic mountain sickness, and the obesity-hypoventilation and sleep apnea syndromes. Pulmonary hypertension develops in these patients because the long-standing vasoconstriction produced by hypoxia causes muscular hypertrophy of the pulmonary arteries and arterioles. These pathologic changes may regress if alveolar hypoxia is corrected and hypoxic pulmonary vasoconstriction is continuously inhibited. Intermittent inhibition of hypoxic pulmonary vasoconstriction does not reverse these pathologic changes. Since patient noncompliance with oxygen therapy makes it difficult to achieve continual relief of alveolar hypoxia, a drug that inhibits hypoxic vasoconstriction may be useful. Experimental findings indicate that hypoxic pulmonary vasoconstriction requires calcium influx and can be inhibited by certain slow-channel calcium blockers. Studies also demonstrate that slow-channel calcium antagonists can attenuate the pulmonary hypertension and right ventricular hypertrophy produced in rats by chronic hypoxia. Recently, two studies have shown that nifedipine inhibits hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease. If further studies demonstrate that these short-term effects are sustained, certain slow-channel calcium blockers may become a useful adjuvant to low-flow oxygen therapy in the treatment of hypoxic pulmonary hypertension.

Barbiturate anesthetics inhibit thromboxane-, potassium-, but not angiotensin-induced pulmonary vasoconstriction.

Administration of the oxidant lipid peroxide tertiary butyl hydroperoxide (t-bu-OOH) in the isolated rabbit lung leads to acute pulmonary vasoconstriction, which is caused by the synthesis of thromboxane. The inhalational anesthetics, halothane, nitrous oxide, and cyclopropane, markedly enhance t-bu-OOH-induced pulmonary vasoconstriction and thromboxane production. The effects of the intravenous (iv) barbiturates thiopental and pentobarbital on t-bu-OOH-induced vasoconstriction were studied. Thiopental completely and pentobarbital partially blocked t-bu-OOH-induced vasoconstriction. Thiopental inhibited t-bu-OOH-induced synthesis of thromboxane and prostacyclin but pentobarbital did not. This inhibitory action of thiopental may be due to its antioxidant properties because similar inhibition has been observed of t-bu-OOH-induced thromboxane production with the antioxidants, vitamin E, or butylated hydroxylanisole. Thiopental and pentobarbital also inhibited the vasoconstriction induced by a thromboxane analog, epoxymethano prostaglandin H2 (U46619). Finally, both barbiturates partially inhibited the pulmonary vasoconstriction caused by potassium chloride, which requires calcium entry, but they did not inhibit the constriction caused by angiotensin II, which does not require calcium entry. These results suggest that pentobarbital and thiopental may block pulmonary vasoconstriction by inhibiting calcium entry.

The Effect of Treatment with Nitrendipine and Other Calcium Channel Blockers on the Physiologic and Pathologic Changes Caused by Hypoxia in Rats

Nitrendipine and other calcium channel blokers acutely inhibit hypoxic pulmonary vasoconstriction and show promise in the prevention of the pulmonary vascular and cardiac changes produced by chronic alveolar hypoxia. This paper reviews the current information available from animal and clinical studies.