Tissue Release of Adenosine Triphosphate Degradation Products During Shock in Dogs

doi:10.1378/chest.97.1.220

Chest

Volume 97, Issue 1, January 1990, Pages 220-226

https://doi.org/10.1378/chest.97.1.220 Get rights and content

Clinical monitoring of cellular metabolism during shock, based largely on traditional metabolic indicators, remains unsatisfactory. The purpose of this study was to compare venous oxygen tension and blood lactate gradients with blood gradients of purine nucleotide degradation products which are derived from tissue ATP catabolism during hypovolemic shock. Sixteen dogs were instrumented to sample arterial and venous blood. Measurements of arteriovenous lactate and PNDP gradients during spontaneous respiration were examined at four tissue sites: gut, kidney, hindlimb, and diaphragm. Hypovolemic shock (mean arterial blood pressure 35 to 40 mm Hg) was induced and maintained for one hour. The above parameters were remeasured at 30 and 60 minutes after induction of shock. Hypoxanthine gradients were greater than that of other PNDP, and so were used as the primary indicator of tissue ATP metabolism. In the hindlimb, the mean AV gradients for hypoxanthine (1 ± 1 μM) were not significantly greater than baseline, while the lactate gradient (700 ± 300 μM) rose markedly. In contrast, across the kidney there was a significantly greater AV hypoxanthine gradient (16 ± 3 μM, p<0.002) but no lactate gradient (-400 ± 200 μM). Both the hypoxanthine and lactate AV gradients were significantly elevated across the diaphragm and gut. Venous Po₂ values less than 35 mm Hg predicted an increased hypoxanthine gradient across the kidney, but not across the hindlimb. We conclude that the metabolic response to hypovolemic shock as assessed by PNDP gradients, lactate gradients, and venous Po₂ differs among tissues. Although resting muscle such as the hindlimb may be an important source of blood lactate, the viscera and working skeletal muscle (the diaphragm) are major contributors to circulating PNDP.

(Chest 1990; 97:220-26)

Section snippets

METHODS

Surgical Preparation

Sixteen mongrel dogs weighing between 12 and 24 kg were fasted overnight. This assured that the stomach would be decompressed to allow for optimal visceral and diaphragmatic catheter placement. They were anesthetized with 30 mg/kg of intravenous pentobarbital. Additional anesthesia was given to prevent shivering, yet allow spontaneous respiration. All dogs were tracheotomized and initially maintained on mechanical ventilation with a tidal volume of 25 ml/kg while further

RESULTS

At baseline, mean AV gradients of all PNDP were 1 μM at each site. Lactate AV gradients did not exceed 200 μM across any tissue bed (renal – 200 ± 100 μM, diaphragm 200 ± 100 μM, femoral 100 ± 100 μM, portal 100 ± 100 μM), and did not differ significantly. Mean baseline values of venous Po₂ were all greater than 40 mm Hg, the renal vein being the highest (67 ± 5 mm Hg) and the femoral lowest (45 ± 3 mm Hg).

During hypotension, arterial levels of the measured PNDP rose only slightly (eg, the mean

DISCUSSION

This study demonstrates important differences between tissues in their metabolic response to hypovolemic shock, as assessed by PNDP gradients, lactate gradients, and venous oxygen tension. Each of these indices reflects a very different aspect of cellular metabolism. Lactate is dependent on the intracellular oxidation/reduction state, while venous oxygen tension in a specific organ effluent reflects mean tissue oxygen tensions.2, 3, 4 The PNDP gradients most likely reflect ATP degradation and

ACKNOWLEDGMENTS:

The authors gratefully acknowledge the expert technical assistance of Fadhil Hussein ana Mark Rosati. The authors also thank Marshal Shlafer, Ph.D. for his critique of the manuscript and Richard H. Simon, M.D. for his helpful suggestions.

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Presented in part as a finalist in the Cecile Lehman Mayer Research Award competition, ACCP Annual Meeting, San Francisco, September 22-26, 1986.

Supported by grants from the American Heart Association, Northeast Ohio Affiliate; the American Heart Association of Michigan; the American Lung Association; and the National Institutes of Health (GCRC: 5-M01RR42; 25S2 and K08-HL01930).

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