16
Non-invasive
venous
assessment
consisted
of
photoplethysmography and venous doppler.
Incompetence of venous circulation was demonstrated, at the saphenofemoral and short saphenopopliteal junctions and at thigh and calf perforators (table). All six patients had rapid venous refilling times (under 12 s, normal 20 s or more). Tissue biopsy of the propositus’ ulcerated legs revealed chronic, non-specific inflammation with histologically normal arteries, arterioles, and veins and venules with no evidence of vasculitis or endothelial injury. The propositus’ lesions did not respond to debridement and skin graft and the ulcers recurred. The leg ulcers in his relatives healed on conservative management. In these eleven related Jews of Iraqi descent the lesions are not typical of commonly found types of chronic ulcer most of which are secondary to incompetence of the deep venous system. The age and sex ratio are also atypical. Neither clinical evidence of varicosities nor the venous studies suggest a venous lesion as the sole cause of the chronic leg ulcerations encountered. Furthermore the
seven
morphological changes typical of venous insufficiency (prominent medial malleolar involvement, oedematous limbs, brawny induration, brownish pigmentation, and dermatitis) were absent. Thromboangiitis obliterans (Buerger’s disease), on whatever criteria,z3 does not fit the picture in the affected members of this kindred. Non-insulin-dependent diabetes can be excluded too, as was thalassaemia.4 Deficiency of G-6-PD has to be considered as a contributory cause, but detailed study of, for example, neutrophil function-if defective this might impair healing of ulcers-was not investigated. The prevalence of G-6-PD deficiency in this kindred may simply reflect the frequency of this enzymatic defect in the Jewish population of Iraq. Laboratory tests showed no evidence of haemolysis and we do not think that G-6-PD deficiency is implicated. This uncommon pattern of chronic leg ulceration of juvenile onset may be associated with a genetic factor, but one which is neither Y-linked nor X-linked. An autosomally transmitted trait expressed in one sex only is said to be sex-limited, as exemplified by precocious puberty.6 In our view an autosomal dominant, sex-linked genetic defect is the most plausible explanation for the prevalence of chronic leg ulcers in the eleven males reported here. REFERENCES 1. Dale JJ, Callam MJ, Ruckley CV, Harper DR, Berrey PN. Chronic ulcers of the leg: a study of prevalence in a Scottish community. Health
Bull 1983; 41: 310-14. 2. Adar R, Papa MZ, Halpern Z, et al. Cellular sensitivity to collagen in thromboangiitis obliterans. N Engl J Med 1983; 308: 1113-16. 3. Shionoya S. Buerger’s disease (thromboangiitis obliterans). In: Rutherford RB, ed. Vascular surgery, 3rd ed. Philadelphia: Saunders, 1989: 207-17. 4. Ganor S, Cohen T. Leg ulcers in a family with both beta thalassaemia and glucose-6-phosphate dehydrogenase deficiency. Br J Dermatol 1976; 95: 203-06. 5. Goodman RM. Genetic disorders among the Jewish people. Baltimore: Johns Hopkins University Press, 1979: 124-70. 6. Thompson JS, Thompson MW. Patterns of single gene inheritance. In: Thompson JS, Thompson MW, eds. Genetics in medicine, 4th ed. Philadelphia: Saunders, 1986: 73-75.
ADDRESSES Departments of Plastic Surgery (E Winkler, A. Shvoron, MD, H Tsur, MD), Medicine (D. Levertowsky, MD), Vascular Surgery (D Chayen, MD), and Genetics Institute late R M Goodman, MD), Chaim Sheba Medical Centre, Hashomer 52621, Israel. Correspondence to Dr Eyal Winkler.
MD, and
(the Tel
Experimental reduction of portal hypertension by mechanical increase of liver portal flow
Studies on the isolated perfused rat liver demonstrated that an increase in portal pressure is associated with an increase in the portal blood flow in normal and in cirrhotic livers. In two pigs with portal hypertension mesenteric portal pressure was lowered by mechanically increasing the liver portal blood flow by means of a balloon pump around the portal vein.
The treatment of portal hypertension has evolved from complete relief via a portal-systemic shunt to less radical approaches, such as injection sclerotherapy, beta blockers, or non-decompressive surgery, which preserve portal flow but have little or no effect on pressure and so do not eliminate the risk of rebleeding. The ideal would be to reduce the pressure and flow in oesophageal varices while increasing the portal blood flow. Two experiments were devised to test the feasibility of this approach. In the first, the relation between portal pressure and liver portal flow was investigated in a cirrhotic rat model. In the second we assessed the ability of a balloon pump to improve liver portal flow and to reduce splanchnic portal pressure in pigs with portal hypertension. Cirrhosis was induced in Sprague-Dawley rats by intraperitoneal injection of 03 ml carbon tetrachloride in mineral oil thrice weekly for 8 weeks. 2 weeks after the last injection portal pressure was recorded by direct puncture. Livers were removed and placed in a recirculating, isolated perfused system. The perfusion solution was oxygenated (0, 95%, CO2 5%), heated (37°C), Krebs albumin (5 g/1) solution (pH 740). Baseline portal flow was measured over 20 min at a perfusion pressure equal to that found in the portal vein before the animal was killed. Portal flow was measured for 15 min at a higher pressure of 25 or 45 cm of H2O. Two 70 kg pigs were anaesthetised and the portal vein was dissected via a bilateral subcostal incision. Portal pressure was recorded via a cannula in a jejunal vein. Another catheter was introduced via the right portal vein stump and advanced into the left branch of the portal vein. Portal flow was measured with a Gould-Statham 2202 flow meter, via a probe placed around the main left branch of the portal vein. Branches of the portal vein were dissected and all of the right and one of the left segmented portal branches were ligated. This raised portal pressure from 13 to 24 mm Hg in the first pig and from 12 to 23 mm Hg in the second, and reduced portal flow from 950 to 700 and from 650 to 180 mlJmin, respectively. At this stage, the Portac (portal accelerator) device was applied around the portal vein. This is an air-driven pump consisting of three pairs of balloons (35 x 11x10 mm) enveloped by a rigid box. The pairs work in a cyclical sequence controlled by computer. Cycle duration (800 ms) and pressure (0-32 bar) applied to the balloons by a compression-vacuum generator were chosen after extensive bench testing on a portal circulation model.
In 15 control
rats
baseline
portal pressure was
10-3
(SD
0-67) cm H20. When pressure was increased to 25 or 45 cm
H2O portal flow rose significantly (table). In 12 cirrhotic rats baseline portal pressure was 13T1 (2-41) cm H2O,
17
TABLE I-RISE IN PORTAL FLOW WITH INCREASED PORTAL PRESSURE IN CONTROL AND CIRRHOTIC RATS
might lead to increased intrahepatic portal-venous shunting rather than increased sinusoidal circulation, exposing the patient to the risk of encephalopathy and worsening liver function. On the other hand it might lead to recruitment of new functional sinusoids or to the improvement of flow in existing ones. Other outstanding questions are whether the portal vein above the pump will be able to tolerate the high pressure without aneurysmal dilatation. Will the reduction in the pressure in the mesenteric side of the portal vein lead increase in intestinal arterial flow or to a reduction in intestinal flow? Despite these doubts and unanswered questions an approach to the management of portal hypertension via mechanical increase in hepatic portal flow merits further research. to an
significantly (p
Non-invasive
venous
assessment
consisted
of
photoplethysmography and venous doppler.
Incompetence of venous circulation was demonstrated, at the saphenofemoral and short saphenopopliteal junctions and at thigh and calf perforators (table). All six patients had rapid venous refilling times (under 12 s, normal 20 s or more). Tissue biopsy of the propositus’ ulcerated legs revealed chronic, non-specific inflammation with histologically normal arteries, arterioles, and veins and venules with no evidence of vasculitis or endothelial injury. The propositus’ lesions did not respond to debridement and skin graft and the ulcers recurred. The leg ulcers in his relatives healed on conservative management. In these eleven related Jews of Iraqi descent the lesions are not typical of commonly found types of chronic ulcer most of which are secondary to incompetence of the deep venous system. The age and sex ratio are also atypical. Neither clinical evidence of varicosities nor the venous studies suggest a venous lesion as the sole cause of the chronic leg ulcerations encountered. Furthermore the
seven
morphological changes typical of venous insufficiency (prominent medial malleolar involvement, oedematous limbs, brawny induration, brownish pigmentation, and dermatitis) were absent. Thromboangiitis obliterans (Buerger’s disease), on whatever criteria,z3 does not fit the picture in the affected members of this kindred. Non-insulin-dependent diabetes can be excluded too, as was thalassaemia.4 Deficiency of G-6-PD has to be considered as a contributory cause, but detailed study of, for example, neutrophil function-if defective this might impair healing of ulcers-was not investigated. The prevalence of G-6-PD deficiency in this kindred may simply reflect the frequency of this enzymatic defect in the Jewish population of Iraq. Laboratory tests showed no evidence of haemolysis and we do not think that G-6-PD deficiency is implicated. This uncommon pattern of chronic leg ulceration of juvenile onset may be associated with a genetic factor, but one which is neither Y-linked nor X-linked. An autosomally transmitted trait expressed in one sex only is said to be sex-limited, as exemplified by precocious puberty.6 In our view an autosomal dominant, sex-linked genetic defect is the most plausible explanation for the prevalence of chronic leg ulcers in the eleven males reported here. REFERENCES 1. Dale JJ, Callam MJ, Ruckley CV, Harper DR, Berrey PN. Chronic ulcers of the leg: a study of prevalence in a Scottish community. Health
Bull 1983; 41: 310-14. 2. Adar R, Papa MZ, Halpern Z, et al. Cellular sensitivity to collagen in thromboangiitis obliterans. N Engl J Med 1983; 308: 1113-16. 3. Shionoya S. Buerger’s disease (thromboangiitis obliterans). In: Rutherford RB, ed. Vascular surgery, 3rd ed. Philadelphia: Saunders, 1989: 207-17. 4. Ganor S, Cohen T. Leg ulcers in a family with both beta thalassaemia and glucose-6-phosphate dehydrogenase deficiency. Br J Dermatol 1976; 95: 203-06. 5. Goodman RM. Genetic disorders among the Jewish people. Baltimore: Johns Hopkins University Press, 1979: 124-70. 6. Thompson JS, Thompson MW. Patterns of single gene inheritance. In: Thompson JS, Thompson MW, eds. Genetics in medicine, 4th ed. Philadelphia: Saunders, 1986: 73-75.
ADDRESSES Departments of Plastic Surgery (E Winkler, A. Shvoron, MD, H Tsur, MD), Medicine (D. Levertowsky, MD), Vascular Surgery (D Chayen, MD), and Genetics Institute late R M Goodman, MD), Chaim Sheba Medical Centre, Hashomer 52621, Israel. Correspondence to Dr Eyal Winkler.
MD, and
(the Tel
Experimental reduction of portal hypertension by mechanical increase of liver portal flow
Studies on the isolated perfused rat liver demonstrated that an increase in portal pressure is associated with an increase in the portal blood flow in normal and in cirrhotic livers. In two pigs with portal hypertension mesenteric portal pressure was lowered by mechanically increasing the liver portal blood flow by means of a balloon pump around the portal vein.
The treatment of portal hypertension has evolved from complete relief via a portal-systemic shunt to less radical approaches, such as injection sclerotherapy, beta blockers, or non-decompressive surgery, which preserve portal flow but have little or no effect on pressure and so do not eliminate the risk of rebleeding. The ideal would be to reduce the pressure and flow in oesophageal varices while increasing the portal blood flow. Two experiments were devised to test the feasibility of this approach. In the first, the relation between portal pressure and liver portal flow was investigated in a cirrhotic rat model. In the second we assessed the ability of a balloon pump to improve liver portal flow and to reduce splanchnic portal pressure in pigs with portal hypertension. Cirrhosis was induced in Sprague-Dawley rats by intraperitoneal injection of 03 ml carbon tetrachloride in mineral oil thrice weekly for 8 weeks. 2 weeks after the last injection portal pressure was recorded by direct puncture. Livers were removed and placed in a recirculating, isolated perfused system. The perfusion solution was oxygenated (0, 95%, CO2 5%), heated (37°C), Krebs albumin (5 g/1) solution (pH 740). Baseline portal flow was measured over 20 min at a perfusion pressure equal to that found in the portal vein before the animal was killed. Portal flow was measured for 15 min at a higher pressure of 25 or 45 cm of H2O. Two 70 kg pigs were anaesthetised and the portal vein was dissected via a bilateral subcostal incision. Portal pressure was recorded via a cannula in a jejunal vein. Another catheter was introduced via the right portal vein stump and advanced into the left branch of the portal vein. Portal flow was measured with a Gould-Statham 2202 flow meter, via a probe placed around the main left branch of the portal vein. Branches of the portal vein were dissected and all of the right and one of the left segmented portal branches were ligated. This raised portal pressure from 13 to 24 mm Hg in the first pig and from 12 to 23 mm Hg in the second, and reduced portal flow from 950 to 700 and from 650 to 180 mlJmin, respectively. At this stage, the Portac (portal accelerator) device was applied around the portal vein. This is an air-driven pump consisting of three pairs of balloons (35 x 11x10 mm) enveloped by a rigid box. The pairs work in a cyclical sequence controlled by computer. Cycle duration (800 ms) and pressure (0-32 bar) applied to the balloons by a compression-vacuum generator were chosen after extensive bench testing on a portal circulation model.
In 15 control
rats
baseline
portal pressure was
10-3
(SD
0-67) cm H20. When pressure was increased to 25 or 45 cm
H2O portal flow rose significantly (table). In 12 cirrhotic rats baseline portal pressure was 13T1 (2-41) cm H2O,
17
TABLE I-RISE IN PORTAL FLOW WITH INCREASED PORTAL PRESSURE IN CONTROL AND CIRRHOTIC RATS
might lead to increased intrahepatic portal-venous shunting rather than increased sinusoidal circulation, exposing the patient to the risk of encephalopathy and worsening liver function. On the other hand it might lead to recruitment of new functional sinusoids or to the improvement of flow in existing ones. Other outstanding questions are whether the portal vein above the pump will be able to tolerate the high pressure without aneurysmal dilatation. Will the reduction in the pressure in the mesenteric side of the portal vein lead increase in intestinal arterial flow or to a reduction in intestinal flow? Despite these doubts and unanswered questions an approach to the management of portal hypertension via mechanical increase in hepatic portal flow merits further research. to an
significantly (p
