Papaverine

Evaluation of the risk factors for ventricular arrhythmias secondary to QT prolongation induced by papaverine injection during coronary flow reserve studies using a 4 Fr angio-catheter.[Pubmed:29713819]

Heart Vessels. 2018 Nov;33(11):1358-1364.

Estimation of the fractional flow reserve (FFR) is considered to be an established method by which to assess stable coronary artery stenosis. Induction of maximal coronary hyperemia is important during the FFR procedure. Papaverine has been reported to increase the risk of ventricular arrhythmia (VA). The purpose of the present study was to discover predictors of Papaverine-induced VAs developing during FFR measurement. A total of 213 clinically stable patients were included in the study. FFRs were determined after intracoronary Papaverine administration (12 mg into the left and 8 mg into the right coronary arteries). We compared patients in whom VA did and did not develop in terms of clinical and electrocardiogram characteristics. FFR measurements were performed on 244 lesions (133 in the left anterior descending arteries, 43 in the left circumflex arteries, and 68 in the right coronary arteries). We found that the QTc interval was prolonged in all patients after Papaverine administration (average post-administration QTc interval = 569 +/- 89 ms; average DeltaQTc interval = 144 +/- 80 ms). VA developed in three patients with significantly prolonged QT intervals (average post-administration QTc interval = 639 +/- 19 ms, average DeltaQTc interval = 220 +/- 64 ms, p < 0.02) and transitioned from torsade de pointes to ventricular fibrillation. Bradycardia (< 50 beats/min), hypokalemia (serum K < 3.5 mEp/L), and low left ventricular function (ejection fraction (EF) < 50%) were associated with VA (bradycardia, p < 0.01; hypokalemia, p < 0.01; low left ventricular function, p < 0.01). Three-vessel disease was significantly predictive of VA (p < 0.003). In the three-vessel group, the complications of low left ventricular function, hypokalemia, and bradycardia were significantly associated with VA (p < 0.045). Three-vessel disease is a predictor of the development of VA during FFR measurement performed with the aid of Papaverine, especially if accompanied by one or more of the following: low left ventricular function, hypokalemia, or bradycardia.

Microstructural characterization of papaverine-loaded HPC/PVA gels, films and nanofibers.[Pubmed:29935349]

Eur J Pharm Sci. 2018 Sep 15;122:9-12.

Papaverine hydrochloride loaded gels, films and electrospun fibers were prepared for buccal drug delivery with the aim of improving the oral bioavailability of the crystalline drug, which can be achieved by the increased solubility and by the circumvention of the intensive first pass metabolism. The water soluble hydroxypropyl cellulose (HPC) was chosen as a mucoadhesive polymer. In order to improve the electrospinnability of HPC, the similarly mucoadhesive poly(vinyl alcohol) (PVA) was used. Since the drying of gels is of decisive role in either the formation of drug-loaded cast films or electrospun fibers, a real time ortho-positronium (o-Ps) tracking of gels was applied in order to obtain information about the supramolecular changes of the drying-induced gel-film transition. An anomalous increase of o-Ps lifetime value in the gel-film transition region was observed which refers to the remaining intramolecularly bound water in the drug-loaded polymeric gel matrix. The latter could provide information about the characteristics of polymer-water interactions in the phase transition, consequently the storage stability of the formulated solid system.

Sinus Standstill in a Patient after Intracoronary Papaverine Administration for a Coronary Fractional Flow Reserve.[Pubmed:29681575]

Int Heart J. 2018 May 30;59(3):630-633.

A 78-year-old woman had paroxysmal atrial fibrillation and effort angina. Two months before she was admitted for a coronary angiography, she had been feeling dizzy. A Holter 24-hour electrocardiography monitor exhibited an asymptomatic episode of 2.9 seconds of RR interval. She underwent a coronary angiography, which showed intermediate stenosis in the left descending artery. Fractional flow reserve (FFR) measurement using intracoronary Papaverine administration was performed. After intracoronary Papaverine (12 mg) administration, pause of 4 seconds led to polymorphic ventricular tachycardia (VT), although the VT terminated spontaneously. Premature ventricular beat occurred and led to sustained polymorphic VT. In cardiac electrophysiology study, pacing from the right atrium showed that the maximum sinus node recovery time (SRT) was 910 ms. After procainamide (10 mg/kg) administration, the maximum SRT was 16.3 seconds with some junctional escapes. After intravenous Papaverine administration, there was a slight change. Intracoronary Papaverine administration induced about 9-seconds pause with some junctional escapes. We conclude that intracoronary Papaverine administration reveals potential sinus node dysfunction. The patient has been asymptomatic since the implantation of the pacemaker. Patients with suspicious sinus dysfunction should be careful.