Biomedical subjects
W R Summer
Publications and source records attributed to W R Summer.
Thromboxane-induced pulmonary vasoconstriction: involvement of calcium.
Infusion of tert-butyl hydroperoxide (t-bu-OOH) or arachidonic acid into rabbit pulmonary arteries stimulated thromboxane B2 (TxB2) production and caused pulmonary vasoconstriction. Both phenomena were blocked by cyclooxygenase inhibitors or a thromboxane synthase inhibitor. The increase in pulmonary arterial pressure caused by either t-bu-OOH or arachidonic acid infusion correlated with the concentration of TxB2 in the effluent perfusate. The concentration of TxB2 in the effluent perfusate, however, was always 10-fold greater after arachidonic acid infusion. In the rabbit pulmonary vascular bed lipoxygenase products did not appear involved in the vasoactive response to t-bu-OOH or exogenous arachidonic acid infusion. Calcium entry blockers or a calcium-free perfusate prevented the thromboxane-induced pulmonary vasoconstriction. Calmodulin inhibitors also blocked the pulmonary vasoconstriction induced by t-bu-OOH without affecting the production of TxB2 or prostacyclin. These results suggest that thromboxane causes pulmonary vasoconstriction by increasing cytosol calcium concentration.
Aminophylline-induced suppression of pulmonary antibacterial defenses.
Respiratory infections are frequently observed in patients with chronic obstructive pulmonary disease, indicating that host defenses are compromised. Antibacterial defenses of the lung against such infections include the alveolar macrophage and polymorphonuclear leukocytes (PMN) that migrate into the lung to provide auxiliary phagocytic defenses. To test the hypothesis that aminophylline acutely impairs pulmonary antibacterial defenses, mice were challenged by aerosol inhalation with Staphylococcus aureus or Proteus mirabilis and injected intraperitoneally with aminophylline (20, 40, or 80 mg/kg). Pulmonary bactericidal activity and total lavaged lung cell and differential counts were determined 4 h after bacterial challenge. The highest dose of aminophylline suppressed the killing of S. aureus so that 55 +/- 5% of the initial viable bacteria remained as compared with 22 +/- 4% in the control animals. In contrast, there was a dose-related suppression of pulmonary antibacterial defenses against gram-negative bacteria. With doses of 40 and 80 mg/kg, lung defenses were ablated, allowing the proliferation of P. mirabilis to 115 +/- 9% and 253 +/- 9%, respectively, the control value being 26 +/- 3%. The number of PMN obtained by lavage after aerosol challenge with P. mirabilis was also inhibited by aminophylline in a dose-dependent manner. From the lungs of untreated animals 5.0 +/- 0.3 X 10(6) PMN were recovered as compared with 3.3 +/- 0.1 X 10(6), 2.5 +/- 0.2 X 10(6), and 1.8 +/- 0.1 X 10(6), respectively, with increasing doses of aminophylline. The bactericidal activity of lavaged PMN from the lungs of aminophylline-treated rats challenged with the gram-negative bacterium in vivo was significantly depressed when compared with that in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Initial aminoglycoside levels in the critically ill.
Twenty-six consecutive patients admitted to the medical ICU with presumed sepsis or septic shock had their initial serum aminoglycoside level determined 1 h after completion of a 20-min infusion of tobramycin, 2 mg/kg. There was a poor correlation between the dose received and the measured aminoglycoside level; 59% of the patients had initial blood aminoglycoside concentrations below the recommended peak level of 5 micrograms/ml. An underestimation of the volume of distribution in critically ill patients best explains the low serum aminoglycoside levels produced by the currently recommended dosage schedule.
Augmentation of cardiac function by elevation of intrathoracic pressure.
We studied the cardiovascular effects of increasing intrathoracic pressure in an acute pentobarbital-anesthetized canine model of acute ventricular failure induced by large doses of propranolol. Left ventricular (LV) function curves were generated by volume loading from LV filling pressures of 5-20 Torr. The animals were ventilated by using intermittent positive-pressure ventilation with large tidal volumes (30 ml/kg). Chest and abdominal pneumatic binders were used to increase intrathoracic pressure. When compared with the control state, acute ventricular failure was associated with a decrease in the slope of the LV function curves (P less than 0.01). After binding the increase in intrathoracic pressure (1.1 +/- 1.6 to 12.1 +/- 2.4 Torr, P less than 0.01) was associated with an improvement in both right ventricular and LV function. Our study demonstrates that in this model of acute ventricular failure, increasing intrathoracic pressure improves cardiac function. We postulate that this observed improvement with increased intrathoracic pressure is due to reduced LV wall stress in a manner analogous to that seen with arterial vasodilator therapy in congestive heart failure.
Cardiac augmentation by phasic high intrathoracic pressure support in man.
Left ventricular performance can be significantly influenced by changes in intrathoracic pressure. In man, sustained increases in intrathoracic pressure unload the left ventricle, but since venous return decreases, increased intrathoracic pressure is associated with a decreased cardiac output. In a canine model of acute ventricular failure, it has been shown that phasic increases in intrathoracic pressure, which do not decrease venous return, improve steady-state cardiac output. We thus studied the cardiovascular effects of phasic high intrathoracic pressure support (PHIPS) in seven patients with shock in our intensive care unit whose condition was not responsive to conventional types of therapy. The PHIPS was generated by abdominal and chest wall binding during positive-pressure ventilation. As compared to the state before PHIPS, the PHIPS was associated with an increase in esophageal pressure (6.6 +/- 1.1 mm Hg; p less than 0.01) and in mean arterial pressure (43.0 +/- 6.1 to 51.0 +/- 7.7 mm Hg; p less than 0.01) while not changing arterial pressure relative to esophageal pressure. Cardiac output also increased from 3.6 +/- 0.5 to 4.2 +/- 0.6 L/min (p less than 0.05), while left ventricular filling pressures remained constant. In one subject a gated cardiac blood pool scan demonstrated a PHIPS-associated increase in ejection fraction and decreased end-diastolic volume. These results are consistent with the hypothesis that PHIPS, by increasing intrathoracic pressure, augments left ventricular performance by reducing left ventricular afterload. This appears to be a promising area for future research.
Pulmonary mechanics and artificial support of the arrested circulation.
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Comparison of the effects of dobutamine, dopamine, and isoproterenol on hypoxic pulmonary vasoconstriction in the pig.
The relative vasodilating properties of isoproterenol, dopamine, and dobutomine on hypoxic pulmonary vasoconstriction were examined in isolated pig lungs, ventilated and perfused in situ. The flow-resistant properties of the pulmonary circulation were assessed by measuring the relationship between pulmonary arterial pressure (PAP) and flow (Q). Hypoxia ( a decrease in inspired O2 tension form 200 torr to 50 torr) caused a rightward shift and decreased in the slope of this relationship. This increase PAP an average of 18.8 torr when measured at a blood flow of 1 L/min. Isoproterenol and dobutamine inhibited hypoxic pulmonary vasoconstriction, whereas dopamine had no effect. Because of its relative freedom from adverse side-effects in clinical trials, dobutamine should be considered in patients with hypoxic pulmonary vasoconstriction and right heart failure.
Clinical decision making with transbronchial lung biopsies. The value of nonspecific histologic examination.
To investigate the importance of fiberoptic bronchoscopy with transbronchial biopsy (TBB) in clinical decision making, we reviewed 242 consecutive TBB procedures with respect to clinical presentation, roentgenographic pattern of disease, bronchoscopy result, and patient outcome. The specific yield of TBB was greatest in patients with multilobar disease and suspected sarcoidosis, metastatic neoplasm, or opportunistic infection. The value of a nonspecific TBB was estimated from its influence in changing clinically-derived suspicions of disease. Using pretest probabilities based on prebronchoscopic suspicions and likelihood ratios derived from our TBB results, Bayes's theorem was applied to estimate posttest probabilities. Nonspecific TBB reduced the probability of granulomatous pneumonitis. However, only small differences in posttest probabilities were associated with this bronchoscopy result in other patients with multilobar infiltrates, and no differences were observed in those with localized disease.
Pulmonary veno-occlusive disease. Morphological changes suggesting a viral cause.
A 47-year-old man with a history of industrial exposure and interstitial lung disease was admitted for acute pulmonary decompensation. Clinical course was characterized by severe dyspnea at rest, fever, hypoxemia, and elevated pulmonary arterial pressures. At autopsy, pulmonary problems were explained by a selective veno-occlusive process. Associated with pulmonary phlebitis was cerebral vasculitis and lymph node enlargement with erythrophagocytosis suggesting underlying viral infection. Pulmonary veno-occlusive disease should be considered in cases of pulmonary fibrosis, pulmonary hypertension with cor pulmonale, and pulmonary edema and congestion with normal left atrial pressures.
Airway response to sublingual nitroglycerin in acute asthma.
To test the efficacy of sublingual nitroglycerin as a bronchodilator, we studied ten patients with acute asthma. After a baseline spirogram, each patient was given 1.2 mg of sublingual nitroglycerin, and subsequent spirograms were obtained a five-minute intervals for 15 minutes. Each patient was then given three subsequent doses of epinephrine (0.5 mg) subcutaneously at 15-minute intervals. Spirograms were obtained 15 minutes after each epinephrine dose. Forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) did not change significantly following sublingual nitroglycerin, but both FEV1 and FVC improved significantly after epinephrine administration. Three patients experienced transient but severe hypotension after receiving sublingual nitroglycerin. The results suggest that sublingual nitroglycerin is not adequate initial therapy for asthmatic attacks and that the administration of sublingual nitroglycerin in acute asthma may be dangerous.
Effects of spontaneous ventilation on the circulation.
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Transbronchial needle aspiration for diagnosis of lung cancer.
Thirty-two consecutive patients with mediastinal lesions suggestive of bronchogenic carcinoma underwent transbronchial needle aspiration. Eighteen of 20 patients (90 percent) with proved bronchogenic carcinoma had malignant cytology specimens or tissue fragments. Of 12 patients with normal cytology specimens, six were subsequently proved to have nonneoplastic disease. Transbronchial needle aspiration appears to offer a sensitive and specific alternative to more invasive surgical techniques used in the diagnosis of malignancies with mediastinal involvement.
Comparison of standard and large forceps for transbronchial lung biopsy in the diagnosis of lung infiltrates.
In order to determine whether larger biopsy forceps improve the diagnostic yield over smaller standard forceps, we performed 30 transbronchial biopsy procedures in 28 patients with lung infiltrates using three types of instruments. We found that compared to the standard forceps specimens the large forceps acquired larger specimens in 22 of 29 procedures and that the alligator forceps acquired larger specimens in 7 of 10 procedures. However, in only 2 of the 29 procedures did the larger biopsy specimen alter the pathologic diagnosis. Four of the patients subsequently underwent open lung biopsy which did not alter the pathologic diagnosis rom the transbronchial biopsy procedure. We conclude that the large forceps do not significantly improve the diagnostic yield of transbronchial biopsy in our patients.
Leftward septal displacement during right ventricular loading in man.
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Catamenial pneumothorax: evaluation by fiberoptic pleuroscopy.
A patient with catamenial pneumothorax and pelvic endometriosis underwent pleuroscopic examination with the flexible bronchoscope. For the first time, using this technique, diaphragmatic defects were observed, and the passage of air through them from the peritoneum to the thoracic cavity was documented.
The effects of acute ethanol ingestion on pulmonary diffusing capacity.
Single breath diffusing capacities for carbon monoxide (DLco) were measured in 12 normal supine subjects before and after ingestion of 15 to 30 ml of 95 percent ethanol (ETOH) to determine if alcohol could acutely change the DLco. Both DLco and specific DLco (DLco/alveolar volume) were significantly decreased 90 minutes after the ingestion of alcohol. This change may be due to a direct effect of alcohol on the alveolar capillary interface by possibly interfering with a carbon monoxide carrier molecule. Another plausible explanation for the reduced diffusing capacity after ingestion of alcohol may be redistribution of blood from the lung to the periphery secondary to the hemodynamic effects of alcohol.