Energy state and vasomotor tone in hypoxic pig lungs.

To evaluate the role of energy state in pulmonary vascular responses to hypoxia, we exposed isolated pig lungs to decreases in inspired PO2 or increases in perfusate NaCN concentration. Lung energy state was assessed by 31P nuclear magnetic resonance spectroscopy or measurement of adenine nucleotides by high-pressure liquid chromatography in freeze-clamped biopsies. In ventilated lungs, inspired PO2 of 200 (normoxia), 50 (hypoxia), and 0 Torr (anoxia) did not change adenine nucleotides but resulted in steady-state pulmonary arterial pressure (Ppa) values of 15.5 +/- 1.4, 30.3 +/- 1.8, and 17.2 +/- 1.9 mmHg, respectively, indicating vasoconstriction during hypoxia and reversal of vasoconstriction during anoxia. In degassed lungs, similar changes in Ppa were observed; however, energy state deteriorated during anoxia. An increase in perfusate NaCN concentration from 0 to 0.1 mM progressively increased Ppa and did not alter adenine nucleotides, whereas 1 mM reversed this vasoconstriction and caused deterioration of energy state. These results suggest that 1) pulmonary vasoconstrictor responses to hypoxia or cyanide occurred independently of whole lung energy state, 2) the inability of the pulmonary vasculature to sustain hypoxic vasoconstriction during anoxia might be associated with decreased energy state in some lung compartment, and 3) atelectasis was detrimental to whole lung energy state.

Pharmacologic therapy of cor pulmonale.

Oxygen remains the mainstay for the therapy of pulmonary hypertension and right ventricular failure in patients with COPD. Oxygen selectively vasodilates the pulmonary vascular bed, increases oxygen delivery and mixed venous oxygen tension, and reduces the elevated pulmonary vascular resistance and right ventricular work. Clinically, oxygen therapy improves neurologic function, exercise performance, and survival. Digitalis therapy is indicated only in patients with biventricular failure or supraventricular tachycardia. Diuretics should be used carefully. Two investigational therapies offer promise, but are unproven. Almitrine increases arterial PO2, and vasodilators lower pulmonary vascular resistance. Despite the proper use of the drugs reviewed in this chapter, the current therapy for the treatment of right ventricular hypertrophy and failure is limited. Improved therapy will require a better understanding of the pathophysiology that causes a hypertrophied ventricle to fail.

31P nuclear magnetic resonance determination of changes in energy state in lung preservation.

The significance of dynamic changes in energy state during lung harvesting and preservation has not been extensively studied. Phosphorus 31 nuclear magnetic resonance spectra at 81 MHz were obtained from degassed rabbit lungs. Changes in the adenosine 5'-triphosphate-to-inorganic phosphate peak-intensity ratios were used to measure changes in energy state. Two groups of rabbit preparations were studied to evaluate the effect of hypothermia during the initial 120 minutes of harvesting (n = 8 at 36 degrees C and n = 5 at 4 degrees C). The significance of these changes was assessed in a second experiment in which lungs were reperfused in vitro at selected intervals of hypothermia (5, 12, and 24 hours) and assessed for injury. Hypothermic preservation sustained a significantly higher energy state. The depletion of energy state was correlated with injury, particularly as measured by lung edema (r2 = -0.715). Short periods of warm ischemia (30 minutes) result in a significant depletion of energy state, which may be a component of pulmonary injury during harvesting and preservation.

31P NMR spectroscopy of isolated perfused lungs.

31P NMR spectra of isolated blood-perfused pig lungs were obtained by degassing the lungs in vivo to remove field inhomogeneities caused by air-tissue interfaces. The spectra show the presence of ATP, phosphodiester, inorganic phosphate, and phosphomonoester, but no phosphocreatine. All the metabolites remained stable for more than 4 h when the lungs were perfused with oxygenated blood. Blood gas tensions, glucose concentration, pH, and temperature were controlled throughout the experiment. During anoxia or ischemia, ATP and intracellular pH declined and Pi increased but returned to control levels during subsequent normoxia or reperfusion. These results demonstrate the applicability of NMR spectroscopy to isolated perfused lungs, enabling studies of metabolic processes in normal and pathologic lungs, as well as establishment of optimal conditions for lung preservation for transplantation.

The application of official policy. Prophylaxis recommendations for patients with mitral valve prolapse.

In 1977, the American Heart Association recommended that patients with mitral valve prolapse (MVP) and mitral insufficiency receive antibiotic prophylaxis prior to procedures that place them at risk for bacterial endocarditis. To study how clinicians conformed to this recommendation, the authors selected 126 patients with MVP admitted to a University Medical Center in 1978, the year following the official policy. Overall, only 47 patients (37%) had the antibiotic prophylaxis recommended. Furthermore, information that might have increased the certainty of diagnosis of MVP or the likelihood of mitral insufficiency did not influence the physician's decision: symptoms, previous history, procedures, sex, evidence for mitral insufficiency, other serious illnesses, or the use of cardiac medications. However, patients seen in consultation by a cardiologist were much more likely to have prophylaxis recommended (P less than 0.05). It was concluded that the application of an official policy about prophylaxis for a condition such as MVP, where the risks are uncertain, is likely to be guided by other factors, such as the opinions of local experts.

Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy.

Over a 10-year period, 276 pulmonary arteriovenous malformations (PAVMs) were occluded with balloon embolotherapy in 76 patients, 67 (88%) of whom had hereditary hemorrhagic telangiectasia. Eleven patients (14%) were discovered by means of family screening with measurement of arterial blood gases and chest radiography. Epistaxis, dyspnea, hemoptysis, and hemothorax occurred in 79%, 71%, 13%, and 9% of patients, respectively. Clinical histories of strokes and transient ischemic attacks were present in 18% and 37% of patients, respectively. Computed tomographic scans of 59 patients showed stroke in 36%. Sixty-five percent of PAVMs were located in the lower lobes, which correlated with the finding of more pronounced hypoxemia in the upright position. After embolotherapy, symptomatic hypoxemia was corrected, and serial values have remained constant for 5 years. Complications were minimal, and no patient required surgery. Balloon embolotherapy is effective long-term therapy for PAVMs, and family screening should be pursued because of the possibility of a higher frequency of paradoxical embolization (stroke) than previously recognized.