Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms.

OBJECTIVES: To ensure the accuracy of susceptibility testing methods for ceftazidime/avibactam. METHODS: The performances of the Etest (bioMérieux), 30/20 µg disc (Hardy diagnostics) and 10/4 µg disc (Mast Group) were evaluated against the reference broth microdilution (BMD) method for 102 clinically relevant Gram-negative organisms: 69 ceftazidime- and meropenem-resistant Klebsiella pneumoniae and 33 MDR non-K. pneumoniae. Essential and categorical agreement along with major and very major error rates were determined according to CLSI guidelines. RESULTS: A total of 78% of isolates were susceptible to ceftazidime/avibactam. None of the three methods met the defined equivalency threshold against all 102 organisms. The Etest performed the best, with categorical agreement of 95% and major errors of 6.3%. Against the 69 ceftazidime- and meropenem-resistant K. pneumoniae, only the Etest and the 10/4 µg disc met the equivalency threshold. None of the three methods met equivalency for the 33 MDR isolates. There were no very major errors observed in any analysis. These results were pooled with those from a previous study of 74 carbapenem-resistant Enterobacteriaceae and data from the ceftazidime/avibactam new drug application to define optimal 30/20 µg disc thresholds using the error-rate bound model-based approaches of the diffusion breakpoint estimation testing software. This analysis identified a susceptibility threshold of ≤19 mm as optimal. CONCLUSIONS: Our data indicate that the Etest is a suitable alternative to BMD for testing ceftazidime/avibactam against ceftazidime- and meropenem-resistant K. pneumoniae. The 30/20 µg discs overestimate resistance and may lead to the use of treatment regimens that are more toxic and less effective.

Viral activity and outcome of hepatitis B surface antigen-positive grafts in deceased liver transplantation.

Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)-positive grafts used to be discarded in the past. The aim of this study was to examine viral activity and outcome of HBsAg-positive deceased grafts transplanted to HBsAg-positive recipients. Eleven HBsAg-positive deceased grafts were transplanted to HBsAg-positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end-stage liver disease score for the recipients was 19 (16-32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg-positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg-positive deceased grafts is feasible and increases the donor pool to rescue dying patients.

Rhabdomyolysis caused by the moderate CYP3A4 inhibitor fluconazole in a patient on stable atorvastatin therapy: a case report and literature review.

WHAT IS KNOWN AND OBJECTIVE: Rhabdomyolysis is a severe potential adverse drug reaction of statin therapy. We report a case of rhabdomyolysis due to drug-drug interaction (DDI) between atorvastatin and fluconazole and review the literature. CASE SUMMARY: A 70-year-old woman received atorvastatin for hyperlipidaemia without any problem for 4 years. When intravenous fluconazole was added for treating a fungal infection, rhabdomyolysis developed 2 weeks later. Removal of atorvastatin led to the resolution of her rhabdomyolysis. WHAT IS NEW AND CONCLUSION: Our case demonstrates that in some subjects even a moderate CYP3A4 inhibitor such as fluconazole may lead to rhabdomyolysis in subjects receiving a statin.

Nicotinic acid and DP1 blockade: studies in mouse models of atherosclerosis.

The use of nicotinic acid to treat dyslipidemia is limited by induction of a "flushing" response, mediated in part by the interaction of prostaglandin D(2) (PGD(2)) with its G-protein coupled receptor, DP1 (Ptgdr). The impact of DP1 blockade (genetic or pharmacologic) was assessed in experimental murine models of atherosclerosis. In Ptgdr(-/-)ApoE(-/-) mice versus ApoE(-/-) mice, both fed a high-fat diet, aortic cholesterol content was modestly higher (1.3- to 1.5-fold, P < 0.05) in Ptgdr(-/-)ApoE(-/-) mice at 16 and 24 weeks of age, but not at 32 weeks. In multiple ApoE(-/-) mouse studies, a DP1-specific antagonist, L-655, generally had a neutral to beneficial effect on aortic lipids in the presence or absence of nicotinic acid treatment. In a separate study, a modest increase in some atherosclerotic measures was observed with L-655 treatment in Ldlr(-/-) mice fed a high-fat diet for 8 weeks; however, this effect was not sustained for 16 or 24 weeks. In the same study, treatment with nicotinic acid alone generally decreased plasma and/or aortic lipids, and addition of L-655 did not negate those beneficial effects. These studies demonstrate that inhibition of DP1, with or without nicotinic acid treatment, does not lead to consistent or sustained effects on plaque burden in mouse atherosclerotic models.

"Left at right" adult liver transplantation: the feasibility of heterotopic implantation of left liver graft.

Left liver grafts have been widely utilized in adult liver transplantation (LT) and yielded acceptable results. However, the conventional orthotopic implantation of a left liver graft imposes the potential risk of perioperative vascular complications. We report herein an alternative modified technique for adult left liver LT and evaluate its feasibility in LT. In this study, 10 recipients had their left liver graft rotated 180°, and heterotopically implanted at the right subphrenic space, which we termed "left at right" liver transplantation (LAR-LT). The sequence of vascular and biliary reconstruction was performed as standard techniques, and no perioperative vascular complications related to LAR-LT were encountered. There were two mortalities in this series, one due to a small-for-size graft dysfunction and the other due to postoperative internal hemorrhage. Two recipients had biliary strictures that were successfully managed by percutaneous biliary dilatation and Roux-en-Y hepaticojejunostomy. The clinical characteristics and outcomes of patients undergoing LAR-LT were also compared with patients undergoing conventional orthotopic left liver LT (n = 14). Although the results showed no significant difference between the two groups, according to our experience, the satisfactory outcome and easier technical reconstruction suggest that the LAR-LT modification could be a feasible alternative to left liver LT.

Hormonal regulation of female reproduction.

Reproduction is an event that requires the coordination of peripheral organs with the nervous system to ensure that the internal and external environments are optimal for successful procreation of the species. This is accomplished by the hypothalamic-pituitary-gonadal axis that coordinates reproductive behavior with ovulation. The primary signal from the central nervous system is gonadotropin-releasing hormone (GnRH), which modulates the activity of anterior pituitary gonadotropes regulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) release. As ovarian follicles develop they release estradiol, which negatively regulates further release of GnRH and FSH. As estradiol concentrations peak they trigger the surge release of GnRH, which leads to LH release inducing ovulation. Release of GnRH within the central nervous system helps modulate reproductive behaviors providing a node at which control of reproduction is regulated. To address these issues, this review focuses on several critical questions. How is the HPG axis regulated in species with different reproductive strategies? What internal and external conditions modulate the synthesis and release of GnRH? How does GnRH modulate reproductive behavior within the hypothalamus? How does disease shift the activity of the HPG axis?

Whole-body vibration for functional constipation: a single-centre, single-blinded, randomized controlled trial.

AIM: The aim of this trial was to determine whether whole-body vibration (WBV) induced via a noninvasive oscillation platform could improve symptoms and health-related quality of life (HRQOL) in patients with chronic functional constipation. METHOD: A single-blinded, randomized controlled trial was performed in a single hospital in Taiwan. Patients diagnosed with chronic functional constipation, as per the Rome III diagnostic criteria, were included and randomized to either the WBV treatment or no treatment (control) group. The treatment group received six 15-min sessions of WBV therapy over a 2-week period. Patients received vibrations of 2 mm in amplitude at a frequency of 12 Hz. The primary outcome was whether constipation symptoms improved, assessed by the constipation severity instrument (CSI) and the secondary outcome measure was whether there was an improvement in HRQOL. RESULTS: Whole-body vibration therapy over a 2-week period in patients with chronic functional constipation (n = 14) significantly reduced the total CSI and obstructive defaecation subscale scores compared with control (n = 13). However, WBV did not improve the pain and chronic inertia subscale scores of the CSI or HRQOL. CONCLUSION: These findings suggest that low-intensity WBV induced via a noninvasive oscillation platform may be an effective therapy for reducing symptom severity in patients with chronic functional constipation.

High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy.

WHAT IS KNOWN AND OBJECTIVE: Teicoplanin and vancomycin show similar clinical and bacteriological efficacy in clinical trials. Teicoplanin has been reported to have a lower adverse drug reaction (ADR) rate than vancomycin. Cross-reactivity between these two glycopeptides is controversial. Our aim was to study the cross-reactivity between teicoplanin and vancomycin through an assessment of all the reported ADRs of these drugs in our University hospital. METHODS: Over a period of 2 years, 170 cases of vancomycin therapy, which were closely monitored by doctors and clinical pharmacists, were used to analyse ADRs. Teicoplanin therapy was used as an alternative in cases of vancomycin intolerance. When an ADR related to vancomycin or teicoplanin was suspected, specialists were consulted to confirm if these were true ADR and to determine whether the implicated drug should be stopped. All ADRs for the two glycopeptides were assessed for causality using the Naranjo probability scale. RESULTS AND DISCUSSION: Thirty-eight of 170 patients (22·4%) treated with vancomycin developed ADRs. Twenty-four patients were switched to teicoplanin. However, 14 of those 24 patients (58·3%) developed ADRs. The time of onset of ADRs involving vancomycin was 12·7 ± 10·9 days (range, 1-46 days). The time of onset of sequential teicoplanin-induced ADRs was 11·7 ± 4·7 days (range, 2-20 days). Of the 14 patients with ADRs related to sequential teicoplanin therapy, six showed cross-reactivity between vancomycin and teicoplanin. The incidence of vancomycin-induced neutropenia was 4·7% (8/170), whereas the incidence of teicoplanin-induced neutropenia subsequent to vancomycin intolerance was as high as 33·3% (8/24). Furthermore, 71·4% (10/14) of the teicoplanin-induced ADRs were associated with haematological abnormalities such as neutropenia, thrombocytopenia or leucopenia. WHAT IS NEW AND CONCLUSION: Teicoplanin, used as an alternative in cases of vancomycin intolerance, was associated with a high incidence of ADRs and haematological reactions, most notably neutropenia. This high rate of ADRs suggests cross-reactivity between the two glycopeptides.

Indicators and outcome of liver transplantation in acute liver decompensation after flares of hepatitis B.

Non-cirrhotic patients having acute liver decompensation in flares of hepatitis B can recover spontaneously or die without liver transplantation. Criteria for identifying patients in need of liver transplantation are lacking. Fifty-one non-cirrhotic patients having acute liver decompensation in flares of hepatitis B were retrospectively reviewed. The patients were divided into three groups: group A patients (n=18) recovered from acute liver decompensation spontaneously; group B patients (n=22) died of acute liver failure; and group C patients (n=11) had liver transplantation. Model of end-stage liver disease (MELD) scores were evaluated to identify the criteria for liver transplantation. The cut-off point of MELD scores for liver transplantation was evaluated by receiver operating characteristic (ROC) curve. Comparing group A and B patients, MELD score was an independent factor to predict prognosis. By analysing ROC curve, a MELD score>30 was the most optimal cut-off point to indicate liver transplantation; however, the false positive rate was 11.1%. By weekly measurement of MELD scores, subsequent increase in MELD scores could help to avoid false positives. Moreover, a MELD score>34 yielded 0% false positive rate and indicated the necessity of definite liver transplantation. For group C patients, ten of 11 patients were saved by liver transplantation. In conclusion, for the patients having acute liver decompensation in flares of hepatitis B, liver transplantation is definitely indicated by MELD scores>34. Liver transplantation is also indicated if the MELD score increases in the subsequent 1-2 weeks. Liver transplantation has a good outcome if performed on time.

Flexible and individualized treatment to achieve sustained viral response for recurrent hepatitis C in liver transplant recipients.

Hepatitis C recurrence after liver transplantation is universal and is a major cause of long-term graft failure. Improving the effectiveness of recurrent hepatitis C treatment is extremely important. We studied 35 anti-hepatitis C virus (HCV)-positive patients who underwent liver transplantation. Among the 35 patients, 25 patients had recurrent hepatitis C and received antiviral treatment. HCV RNA load after liver transplantation was increased by 3.68-fold. The antiviral treatment regimen comprised pegylated-interferon (180 µg) every 2 weeks and ribavirin at a dose of 200-400 mg every day. The treatment duration was flexible and individualized, and depended on viral response to treatment. The dosage of tacrolimus was decreased gradually to minimize immunocompromise. Median (interquartile) serum level of tacrolimus was 6.9 (6-8.9) ng/mL at initiation of treatment and 3.8 (3.6-5) ng/mL at the end of treatment. One patient (4.0%) was withdrawn from the study, and three patients (12%) died of infection during treatment. At end of treatment, 18 of 25 patients (72%) were negative for serum HCV RNA. After an additional 6 months following the end of treatment, 16 of the 25 patients (64%) had sustained viral response (SVR) and only two patients had HCV relapse. The 1-year, 3-year and 5-year survival rates were 91.4%, 84.5% and 84.5% for all patients and 88.0%, 82.8% and 82.8% for the 25 patients who received antiviral therapy. In conclusion, recurrent HCV infection is an important issue in liver transplantation. The flexible regimen of antiviral therapy and individualized immunosuppressive agents that was applied in this study achieved a SVR rate of 64%.

Right hepatectomy by the anterior method with liver hanging versus conventional approach for large hepatocellular carcinomas.

BACKGROUND: The aim was to compare short-term results of right hepatectomy using the anterior approach (AA) and liver hanging manoeuvre with the conventional approach (CA) for large hepatocellular carcinoma (HCC). METHODS: This was a retrospective review of 71 consecutive patients with HCC at least 5 cm in diameter who underwent curative right hepatectomy using either the AA with the liver hanging manoeuvre (33) or the CA (38) between January 2004 and December 2008. Clinical data, operative results and survival outcomes were analysed. RESULTS: The groups had similar clinical, laboratory and pathological parameters. The AA group had larger tumours than the CA group (P = 0.039), but comparable grade and stage distribution. The operative results were similar except for an increased blood transfusion requirement with the conventional procedure (P = 0.001). The AA group had a lower recurrence rate (P = 0.003) and better disease-free survival (DFS) (P = 0.001) than the CA group, but overall survival rates were not significantly different (P = 0.091). Presence of tumour encapsulation, absence of tumour microvascular invasion and AA were predictive of DFS, whereas tumour stage was the only independent predictor of overall survival. CONCLUSION: The AA right hepatectomy with liver hanging manoeuvre for large HCC is associated with reduced blood transfusion requirement and lower recurrence rates in the short term.

Teicoplanin-induced hypersensitivity syndrome with a preceding vancomycin-induced neutropenia: a case report and literature review.

Hypersensitivity syndrome associated with teicoplanin has rarely been reported. We report a case with a preceding episode of vancomyin-related neutropenia. A 47-year-old female with cervical spine infection was treated with vancomycin. Neutropenia occurred after 17 days of vancomycin therapy. Vancomycin was changed to teicoplanin, and the neutropenia resolved 4 days later. After 11 days of teicoplanin therapy, a new episode of hypersensitivity syndrome manifested as fever, bilateral neck lymphadenopathy, mild wheezing, hepatitis and increased CRP occurred. Neutropenia and thrombocytopenia developed 3 days later. The patient's symptoms settled over 1 week following withdrawal of teicoplanin. Naranjo's ADR algorithm categorized the neutropenia associated with vancomycin and the hypersensitivity syndrome associated with teicoplanin as 'probable'.

Meperidine-induced serotonin syndrome in a susceptible patient.

We present a patient with a history of clomipramine-induced serotonin syndrome 5 yr prior who developed serotonin syndrome after a single dose of meperidine. This report heightens appreciation of population at risk and also recognition of potential toxicity in meperidine.

Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance.

To determine the function of VGF, a secreted polypeptide that is synthesized by neurons, is abundant in the hypothalamus, and is regulated in the brain by electrical activity, injury, and the circadian clock, we generated knockout mice lacking Vgf. Homozygous mutants are small, hypermetabolic, hyperactive, and infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AGRP) expression. Furthermore, VGF mRNA synthesis is induced in the hypothalamic arcuate nuclei of fasted normal mice. VGF therefore plays a critical role in the regulation of energy homeostasis, suggesting that the study of lean VGF mutant mice may provide insight into wasting disorders and, moreover, that pharmacological antagonism of VGF action(s) might constitute the basis for treatment of obesity.

Luteinizing hormone-releasing hormone I (LHRH-I) and its metabolite in peripheral tissues.

Luteinizing hormone-releasing hormone (LHRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive system through its initiation of pituitary gonadotropin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of many structural variants with a variety of roles in both the brain and peripheral tissues. Enormous interest has been focused on LHRH-I and LHRH-II and their cognate receptors as targets for designing therapies to treat cancers of the reproductive system. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth and sixth bond of the decapeptide (Tyr(5)-Gly(6)) to form LHRH-(1-5). We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its processed peptide, LHRH-(1-5). Furthermore, LHRH-(1-5) has also been shown to be involved in cell proliferation. This review will focus on the possible roles of LHRH and its processed peptide, LHRH-(1-5), in non-hypothalamic tissues.

Suspect the donor with potential infection in the adult deceased donor liver transplantation.

INTRODUCTION: Liver transplantation is the treatment of choice for end-stage liver disease. However, the shortage of donors is still the major problem in most Asian countries. Using extended donor criteria may maximize the deceased donor pool, but some high-risk donors may show adverse recipient outcomes due to preexisting infection. MATERIALS AND METHODS: This study included deceased donor liver transplant patients from June 2002 through June 2007. We retrospectively reviewed the clinical manifestations of donors and recipients. The donors showed no definite infection at the time the organs were matched to the recipients. Routine sputum, urine, blood, and bile cultures were obtained from the donor during the perioperative period. According to the final reports of the cultures, the recipients divided into two groups: donor infection (DI) and no donor infection (NDI). RESULTS: This study included 59 donor and 72 recipients, including 34 who received a graft from a donor with a positive culture (47.2%) finally, defined as the DI groups, and 38 recipients (52.8%) as the NDI group. Most of them had positive sputum cultures, followed by urine cultures. Staphylococcus aureus was the most common pathogen. Using a stepwise logistical regression model to analyze the significant donor characteristics, donor admission to the intensive care unit (ICU) for 7 days or longer (P < or = .0001), previous cardiopulmonary cerebral resuscitation (CPCR) (P = .036), and inotropic agents (P = .022) were the only three independent factors to predict donor infection. To compare the outcomes between DI and NDI groups, the days of recipient ICU or hospital admission, the 1-week or 1-month mortality rate, and the overall survival showed no significant difference between both groups. However, the hospital mortality rate was mildly higher in the DI group (P = .050). CONCLUSION: Donors with prolonged ICU admissions, rescue by CPCR, and use of inotropic agents carried an high risk of potential infections. Our data did not show a significant increase in adverse outcomes if the recipient received a graft from a potentially infected donor. However, there may be an increased risk of hospital mortality. We should be careful in using these potentially infected donors in selective recipients.

Endoscopic management of biliary complications after adult right-lobe living donor liver transplantation without initial biliary decompression.

OBJECTIVES: We sought to examine biliary complications in adult right-lobe living donor liver transplantation (LDLT) with duct-to-duct anastomosis (RL-LDLT-DD), evaluating the efficacy of endoscopic retrograde cholangiography (ERC) in the diagnosis and management of biliary complications following LDLT. METHODS: Ninety adult RL-LDLT-DD were performed from June 2004 to August 2007, including 21 (23.3%) cases of biliary complications. RESULTS: The endoscopic retrograde cholangiopancreatiography (ERCP) findings were stricture only (n = 8), stricture plus leakage (n = 9), and leakage only (n = 4). In the overall 13 cases of leakage, nine patients recovered after treatment by stent or endoscopic nasobiliary drainage. The time to resolution was 3.0 +/- 1.3 months with 2.2 +/- 1.3 endoscopic examinations. All bile duct complications were treated by ERC first. Among 17 cases with stricture, seven cases were successfully treated by endoscopy and three cases by percutaneous transhepatic cholangiography plus stent (PTCS). In the other seven cases, the treatment was still ongoing in five cases and two subjects died during treatment. The mean time to stricture resolution 7.2 +/- 3.3 months with 3.9 +/- 1.4 endoscopic examinations. The results of 21 cases were 5/21 mortalities (23.8%), successful ERC treatment in 9/21; (42.9%), successful PTCS treatment in 3/21 (14.3%), and ongoing ERC treatment in 5/21, (23.8%), including one case with successful ERC treatment who died of lung infection postoperatively. During follow-up (13.1 +/- 9.9 months), there was no recurrence in the stricture or leak. CONCLUSIONS: When compared with the literature, RL-LDLT-DD without biliary drainage does not increase the incidence of biliary complications. From our study, ERC and PTC play a complementary roles in the treatment of bile duct complications.

IL-37 suppresses migration and invasion of gallbladder cancer cells through inhibition of HIF-1α induced epithelial-mesenchymal transition.

OBJECTIVE: Gallbladder carcinoma (GBC) is the seventh most common cancer across the globe and the most common malignancy of the biliary tract. Epithelial-mesenchymal transition (EMT) is an important pre-requisite for tumor metastasis; however, its mechanism in GBC has not yet been defined. In the present study, we investigated the effects of interleukin-37 (IL-37) on the epithelial-mesenchymal transition (EMT) of gallbladder cancer cells. MATERIALS AND METHODS: RT-qPCR and Western blotting were used to determine the expression of IL-37 in GBC cancer cells and non-tumorigenic human intra-hepatic biliary epithelial cell line. Western blotting was also used for detecting the expression of vimentin, Snail, and E-cadherin. RESULTS: Expression level of IL-37 in GBC cells was decreased in GBC cancer cells compared with the non-tumorigenic human intra-hepatic biliary epithelial cell line. Decreased expression of vimentin and Snail and increased expression of E-cadherin were found in the groups which overexpress IL-37 when compared with the control. Mechanism study showed that IL-37 suppressed the expression of HIF1α in cells. However, HIF1α stabilization by CoCl2 could attenuate the function of IL-37. CONCLUSIONS: Our results indicate that IL-37 plays an antitumor role during the progression of gallbladder carcinoma. IL-37 could inhibit HIF1α induced EMT. Our data provide a new strategy for the treatment of gallbladder cancer.

Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route.