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Delivery of 14C-lignocaine and blood flow to canine organs after coronary occlusion: a physical separation technique to measure drug concentration and microsphere blood flow in the same tissue sample

The purpose of this study is to characterise the distribution of lignocaine relative to blood flow in several organs after coronary occlusion in the dog. To achieve this, it was necessary to develop a convenient, new technique to measure microsphere blood flow and l4C-lignocaine in the same small ti...

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Published in:Cardiovascular research 1982-06, Vol.16 (6), p.331-338
Main Authors: WEINTRAUB, WILLIAM S, HALGASH, DORIS A, PATTERSON, RANDOLPH E
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PATTERSON, RANDOLPH E
description The purpose of this study is to characterise the distribution of lignocaine relative to blood flow in several organs after coronary occlusion in the dog. To achieve this, it was necessary to develop a convenient, new technique to measure microsphere blood flow and l4C-lignocaine in the same small tissue sample. Seven anaesthetised, open-chest dogs were studied after coronary occlusion. Two minutes after occlusion 14C-lignocaine was injected, 75 mg (150 μCi) iv in four dogs (Group II). Three minutes after coronary occlusion radioactive microspheres were injected into the left atrium in order to measure tissue blood flow. Each animal was sacrificed 12 min after coronary occlusion, and samples were removed rapidly from heart, brain, abdominal wall muscle, liver and kidney. After counting each tissue sample in a gamma well counter for microsphere activity, we then dissolved each tissue sample completely. The "supernatant" contained 14C-lignocaine but not microsphere gamma activity because microspheres settled to the bottom of the tube according to their specific gravity of 1.28. Thus, the "supernatant" could be used to measure 14C-lignocaine by liquid scintillation counting. Group I dogs received gamma-labelled microspheres but no 14C-lignocaine and showed no 14C activity when the “supernatants” of their samples were counted in the liquid scintillation counter. Tissue blood flow was highest in kidney and lowest in skeletal muscle, while 14C-lignocaine concentration was highest in liver and lowest in muscle. Although lignocaine concentration correlated significantly with organ blood flow (r = 0.46, P
doi_str_mv 10.1093/cvr/16.6.331
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To achieve this, it was necessary to develop a convenient, new technique to measure microsphere blood flow and l4C-lignocaine in the same small tissue sample. Seven anaesthetised, open-chest dogs were studied after coronary occlusion. Two minutes after occlusion 14C-lignocaine was injected, 75 mg (150 μCi) iv in four dogs (Group II). Three minutes after coronary occlusion radioactive microspheres were injected into the left atrium in order to measure tissue blood flow. Each animal was sacrificed 12 min after coronary occlusion, and samples were removed rapidly from heart, brain, abdominal wall muscle, liver and kidney. After counting each tissue sample in a gamma well counter for microsphere activity, we then dissolved each tissue sample completely. The "supernatant" contained 14C-lignocaine but not microsphere gamma activity because microspheres settled to the bottom of the tube according to their specific gravity of 1.28. 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Thus, the "supernatant" could be used to measure 14C-lignocaine by liquid scintillation counting. Group I dogs received gamma-labelled microspheres but no 14C-lignocaine and showed no 14C activity when the “supernatants” of their samples were counted in the liquid scintillation counter. Tissue blood flow was highest in kidney and lowest in skeletal muscle, while 14C-lignocaine concentration was highest in liver and lowest in muscle. Although lignocaine concentration correlated significantly with organ blood flow (r = 0.46, P&lt;0.05), the correlation was not strong because cumulative tissue uptake (estimated by the index, lignocaine/blood flow) was increasing as blood flow decreased below 0.50 cm3·min−1·g−1. We conclude that this convenient technique should improve the design of experiments by measuring blood flow and 14C drug concentration in the same small tissue sample, using widely available instrumentation. These measurements may clarify the mechanisms of the therapeutic and toxic effects of drugs, hormones and other physiological mediators, particularly in situations where regional blood flow distribution might be abnormal.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>7105099</pmid><doi>10.1093/cvr/16.6.331</doi><tpages>8</tpages></addata></record>
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subjects Animals
Carbon Radioisotopes
Coronary Disease - metabolism
Coronary Disease - physiopathology
Dogs
Lidocaine - metabolism
Methods
Microspheres
Regional Blood Flow
title Delivery of 14C-lignocaine and blood flow to canine organs after coronary occlusion: a physical separation technique to measure drug concentration and microsphere blood flow in the same tissue sample
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