Hemodynamic study during transdermal application of nitroglycerin tape in patients with cirrhosis
Corresponding Author
Tadashi Iwao M. D.
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Second Department of Medicine, Asahi-Machi 67, Kurume-Shi, Fukuoka-Ken, Japan (830)===Search for more papers by this authorAtsushi Toyonaga
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorMichihiro Sumino
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorKohsuke Takagi
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorKazunori Ohkubo
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorRintaroh Inoue
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorKyuichi Tanikawa
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorCorresponding Author
Tadashi Iwao M. D.
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Second Department of Medicine, Asahi-Machi 67, Kurume-Shi, Fukuoka-Ken, Japan (830)===Search for more papers by this authorAtsushi Toyonaga
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorMichihiro Sumino
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorKohsuke Takagi
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorKazunori Ohkubo
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorRintaroh Inoue
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorKyuichi Tanikawa
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Search for more papers by this authorAbstract
We studied 14 patients with portal hypertension and cirrhosis using portal and hepatic vein catheterizations to determine the effects of transdermal application of nitroglycerin tape (containing 10 mg of nitroglycerin and capable of releasing 6 to 7 mg of nitroglycerin in 12 hr) on splanchnic hemodynamics. Patients randomly received nitroglycerin (n = 7) or a placebo (n = 7). No significant changes were observed after the administration of the placebo. In contrast, transdermal nitroglycerin caused a significant reduction in portal pressure, as evaluated by measurements of the portal venous pressure gradient (−22%, p < 0.01). The reduction of portal pressure was due to a decrease in the portal venous pressure, with no changes in the free hepatic venous pressure. Despite the fall in portal pressure, the hepatic blood flow was maintained. These findings suggest that transdermal nitroglycerin could be potentially useful in the treatment of portal hypertension associated with cirrhosis. (HEPATOLOGY 1991;13:124–128).
References
- 1 Needleman P, Johnson EM Jr. Mechanism of tolerance development to organic nitrates. J Pharmacol Exp Ther 1973; 184: 709–715.β
- 2 Blei AT, Friedman S, Gottstein J, Robertson G, Fung HL. Pharmacokinetic-hemodynamic interactions between vasopressin and nitroglycerin: comparison between intravenous and cutaneous routes of nitrate delivery. HEPATOLOGY 1985; 5: 264–270.
- 3 Blei AT, O'Reilly DJ, Gottstein J. Portal-systemic shunting and the hemodynamic effects of nitroglycerin in the rat. Gastroenterology 1984; 86: 1428–1436.
- 4 Kroeger RJ, Groszmann RJ. The effect of the combination of nitroglycerin and propranolol on splanchnic and systemic hemodynamics in a portal hypertensive rat model. HEPATOLOGY 1985; 5: 425–430.
- 5 Gibson PR, McLean AJ, Dudley FJ. The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension. J Gastroenterol Hepatol 1986; 1: 201–206.
- 6 García-Tsao G, Groszmann RJ. Portal hemodynamics during nitroglycerin administration in cirrhotic patients. HEPATOLOGY 1987; 7: 805–809.
- 7 Okuda K, Suzuki K, Musha H, Arimizu N. Percutaneous transhepatic catheterization of the portal vein for the study of portal hemodynamics and shunts: a preliminary report. Gastroenterology 1977; 73: 279–284.
- 8 Pugh RNH, Murray-Lyon M, Dawson JL, Pietroni MC, Williams R. Transection of oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646–649.
- 9 Groszmann RJ, Glickman M, Blei AT, Storer E, Conn HO. Wedged and free hepatic venous pressure measured with a balloon catheter. Gastroenterology 1979; 76: 253–258.
- 10 Vileneuve JP, Huot R, Marleau D, Huet PM. The estimation of hepatic blood flow with indocyanine green: comparison between the continuous infusion and single injection methods. Am J Gastroenterol 1982; 77: 233–237.
- 11 Navasa M, Bosch J, Reichen J, Bru C, Mastai R, Zysset T, Silva G, et al. Effects of verapamil on hepatic and systemic hemodynamics and liver function in patient with cirrhosis and portal hypertension. HEPATOLOGY 1988; 8: 850–854.
- 12 Navasa M, Chesta J, Bosch J, Rodés J. Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis: effects on splanchnic and systemic hemodynamics and liver function. Gastroenterology 1989; 96: 1110–1118.
- 13 Morimoto S, Sekiguchi M, Hirosawa K, Idzu G. Nitroglycerin tape application test in healthy males: report 1 changes in plasma nitroglycerin levels, their effects on the cardiovascular system and adverse reaction [abstract]. Cardioangiology 1984; 16: 298.
- 14 Idzu G, Ishibashi M, Miyazaki H. Determination of glyceryl trinitrate in human plasma by gas chromatography-negative ion chemical ionization-selected ion monitoring. J Chromatogr 1982; 229: 327–336.
- 15 Groszmann RJ, Kravetz D, Bosch J, Glickman M, Bruix J, Bredfeldt J, Conn HO, et al. Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension. HEPATOLOGY 1982; 2: 757–762.
- 16 Viallet A, Marleau D, Huet M, Martin F, Farley A, Villeneuve JP, Lavoie P. Hemodynamic evaluation for patients with intrahepatic portal hypertension: relationship between bleeding varices and the portohepatic gradient. Gastroenterology 1975; 69: 1297–1300.
- 17 Vinel JP, Cassigneul J, Levade M, Voight JJ, Pascal JP. Assessment of short-term prognosis after variceal bleeding in patients with alcoholic cirrhosis by early measurement of portohepatic gradient. HEPATOLOGY 1986; 6: 116–117.
- 18 Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. HEPATOLOGY 1985; 5: 419–424.
- 19 Rigau J, Bosch J, Bordas JM, Navasa M, Mastai R, Kravetz D, Bruix J, et al. Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage. Gastroenterology 1989; 96: 873–880.
- 20 Staritz M, Poralla T, Meyer zum Büschenfelde K-H. Intravascular oesophageal variceal pressure (IOVP) assessed by endoscopic fine needle puncture under basal conditions, Valsalva's manoeuvre and after glyceryltrinitrate application. Gut 1985; 26: 525–530.
- 21 Abrams J. Nitroglycerin and long-acting nitrates. N Engl J Med 1980; 302: 1234–1237.
- 22 Elkayam U, Kulick D, McIntosh N, Roth A, Hsueh W, Rahimtoola SH. Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure. Circulation 1987; 76: 577–584.
- 23 Parker JO, Fung HL. Transdermal nitroglycerin in angina pectoris. Am J Cardiol 1984; 54: 471–476.
- 24 Thadani U, Hamilton SF, Olson E, Anderson J, Voyles W, Prasad R, Teague SM. Transdermal nitroglycerin patches in angina pectoris: dose titration, duration of effect, and rapid tolerance. Ann Intern Med 1986; 105: 485–492.
- 25 Packer M, Medina N, Yushak M, Lee WH. Hemodynamic factors limiting the response to transdermal nitroglycerin in severe chronic congestive heart failure. Am J Cardiol 1986; 57: 260–267.
- 26 Jugdutt BI, Warnica W. Tolerance with low dose intravenous nitroglycerin therapy in acute myocardial infarction. Am J Cardiol 1989; 64: 581–587.