[Evidence of indocyanine green fluorescence in robotically assisted colorectal surgery : What is the status?] / Evidenz der Indocyaningrünfluoreszenz in der robotisch assistierten Kolorektalchirurgie : Wie ist der Status?

BACKGROUND: Indocyanine green (ICG) fluorescence imaging is increasingly being used in various areas of abdominal surgery. The constant improvement in the technology enables easy intraoperative use and progressively influences operative decision-making, also in robotically assisted colorectal surgery. OBJECTIVE: Summation of current evidence on the use of ICG fluorescence imaging in robotically assisted colorectal surgery. MATERIAL AND METHODS: The assessment of evidence is based on a comprehensive literature search (PubMed). RESULTS: First individual studies (feasibility, case matched, prospective cohort, multicenter phase II, single center randomized controlled study/trial) showed a significant reduction in the incidence of anastomotic leakage (AL) after colorectal anastomosis through the use of ICG fluorescence angiography (FA, 9.1% vs. 16.3%; p = 0.04). First feasibility studies demonstrated lymph node detection or navigation as well as ureter visualization. CONCLUSION: The ICG-FA reliably detects tissue perfusion, quickly and effectively with few side effects. It can influence intraoperative decision-making and reduce AL rates. In addition, patients may be offered more precise tumor therapy via ICG sentinel lymph node (SLN) detection and lateral pelvic lymph node (LPN) mapping and navigation. Iatrogenic lesions, such as ureteral injuries can be sufficiently prevented by appropriate visualization; however, valid data in order to be able to derive standardized operative consequences require further convincing multicenter, randomized controlled trials (mRCT).

HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life.

PURPOSE: HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality. MATERIAL AND METHODS: Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires. RESULTS: Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032). CONCLUSION: HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting.

[Intestinal stomata]. / Intestinale Stomata.

An intestinal stoma (greek στὁµα, stoma: mouth, opening) is a surgically created opening of a gut section through the abdominal wall, which serves as an artificial intestinal exit for excretion of feces (synonym preternatural anus). A stoma of the gastrointestinal (GI) tract is often surgically created at the distal small intestine (ileostomy) and the colon (colostomy). Temporary or permanent deviation of fecal excretion may be required to treat various pathological conditions (e.g. congenital anomalies, ileus, inflammatory bowel diseases, posttraumatic, diverticulitis, colorectal malignancy). The creation of an end vs. a loop stoma is technically different. To achieve sufficient patient satisfaction close collaboration between surgeons, professional stoma care with guidance and training as well as support from self-help groups are required. In this way serious stoma-related complications can be avoided.

[Robot-assisted operations in visceral surgery]. / Roboterassistierte Operationen in der Viszeralchirurgie.

BACKGROUND: Although only a low percentage of abdominal surgical interventions are performed using a robotic platform, the total number has significantly increased in recent years and robotic surgery (RS) is no longer limited only to university hospitals. Despite the increasing popularity and many innovations in the field of robotic surgery with new devices, the data situation is confusing. OBJECTIVE: This review deals with the current areas of application of robotic devices in abdominal surgery and whether there are any advantages compared to laparoscopic surgery (LS). MATERIAL AND METHODS: The current international literature was evaluated and is critically discussed with a particular focus on clinical trials. RESULTS: While the disadvantages include high costs and longer times of surgery, the advantages are a stable optical platform and the high mobility even in confined spaces; however, no high-quality, randomized controlled trial in abdominal surgery is currently available that could demonstrate an advantage of RS compared to LS. CONCLUSION: Although no clear advantages of RS for the patients could so far be demonstrated, it seems to be at least equivalent to LS. Undisputed is the level of comfort for the surgeon. Once the costs of RS can be reduced, LS will probably be replaced for most indications.

[Implementation of a fast track program : Challenges and solution approaches]. / Implementierung eines Fast-Track-Programmes : Herausforderungen und Lösungsansätze.

BACKGROUND: For more than a decade the evolving concept of fast track surgery has been implemented, predominantly in colorectal surgery. The practice of fast track surgery has yielded excellent results concerning reduction of postoperative complications and hospital stay and has been shown to increase patient satisfaction; however, several studies have shown a sometimes alarmingly low rate of implementation of the individual fast track measures and the rate is a maximum of 44%. OBJECTIVE: In this review, obstacles for implementation of fast track surgery are investigated. Advice is given on possible solutions to circumvent obstacles and facilitate successful establishment of multimodal recovery protocols in individual institutions. MATERIAL AND METHODS: The current international literature is critically evaluated and discussed with a particular focus on prospective clinical trials and expert recommendations. RESULTS: The reasons for a lack of adherence to fast track surgery principles have been shown to be multifactorial. Time-consuming expenditure, logistic difficulties, lack of support by colleagues as well as limitations in the healthcare system and patient-dependent factors appear to complicate implementation of fast track programs. CONCLUSION: Successful implementation and long-term perpetuation can be achieved only by an interdisciplinary team with a low level hierarchy, continuous training and a positive feedback culture. An early inclusion and clarification of personnel and patients should be firmly integrated into the fast track concept. This results in a higher satisfaction of patients and personnel and subsequently stronger adherence to the fast track concept.

[Mechanical bowel obstruction in geriatric patients : Etiology and perioperative morbidity/mortality compared with a younger cohort]. / Der mechanische Ileus bei geriatrischen Patienten : Ätiologie und perioperative Morbidität/Mortalität im Vergleich zu einer jüngeren Patientenkohorte.

BACKGROUND: Mechanical bowel obstruction is a common condition in geriatric patients in the emergency department. It accounts for up to 50% of all emergency surgeries in the elderly. In recent years, diagnosis and treatment of mechanical bowel obstruction has improved, but little is known whether elderly patients benefit from modern treatment approaches. OBJECTIVE: The aim of the work is to generate knowledge about possible improvement of diagnosis and treatment of mechanical bowel obstruction in the elderly. METHODS: A retrospective review of 132 patients was performed comparing geriatric (>80 years of age) and nongeriatric patients (50-70 years of age) admitted with mechanical bowel obstruction. Etiology, time from first contact to operation, bowel resection rate and morbidity/mortality were compared. Data analysis included Fisher's test and Student t­test. RESULTS: In patients under 70 years of age it took 18.23 ± 0.79 h from first contact until laparotomy in the operating room (OR) vs. 43.38 ± 12.08 h in patients above 80 years of age (p = 0.0111). In 58.9% of geriatric patients, resection of bowel was necessary, while only 35.3% of <70-year-old patients needed bowel resection (p = 0.0401). In all, 50% of geriatric patients experienced major complications (Dindo/Clavien >IIIB) vs. only 12.7% of 50- to 70-year-old patients (p = 0.0002). Postoperative stay in the intensive care unit was significantly prolonged in geriatric patients compared to younger patients (93.97 ± 17.36 h vs. 26.11 ± 3.73 h, p < 0.0001). CONCLUSIONS: Time from first contact in the emergency department until laparotomy in the OR is prolonged in geriatric patients, leading to a higher probability of bowel resection with greater morbidity and mortality. Diagnostics should be intensified and accelerated in geriatric patients. Emergency surgery should be considered earlier.

[Posthepatectomy Liver Failure in Extended Liver Resections: An Overview Based on a Retrospective Single-Centre Analysis]. / Postoperatives Leberversagen nach erweiterten Leberresektionen - eine Übersicht, gestützt durch eine retrospektive Single-Center-Analyse.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most serious complications after major liver resections and an important factor in terms of perioperative morbidity and mortality. Despite many advances in the understanding and grading of PHLF, the definitions found in literature are very heterogeneous, which complicates the identification of high-risk patients. In this study we analysed the results of extended liver resections and potential risk factors for PHLF based on patient data derived from our tertiary referral centre. The aim of the study was to gain an overview of the essential aspects in the prevention of PHLF combined with key intraoperative issues and postoperative treatment strategies. METHODS: We analysed data from 202 patients who underwent extended elective liver resections at our centre between April 1989 and September 2009 (135 right hemihepatectomies, 39 left hemihepatectomies, 28 right trisectionectomies). According to Balzan's "50/50 criteria", PHLF was defined as prothrombin time (PT) < 50 % combined with serum bilirubin (SB) > 50 micromol/L on postoperative day (POD) 5 or as death due to primary or secondary liver failure. RESULTS: Thirty-day mortality and overall in-hospital mortality were 4.95 and 8.91 %, respectively. Twenty-eight (14 %) patients developed PHLF and 16 (57 %) patients died. Compared to patients with normal postoperative liver function, several significant pre- and intraoperative factors for PHLF were identified, e.g. primary malignant liver tumour (p < 0.001), extended liver resection (p < 0.001), time of surgery (p < 0.001) and intraoperative transfusion of packed RBC (p < 0.02) or FFP (p < 0.001). CONCLUSION: Although progress has been made in hepatobiliary surgery, PHLF remains a serious complication, especially after extended liver resections. Careful, optimised preoperative risk stratification is required to identify patients at risk for PHLF.

[Implementation of the Perioperative WHO Safety Checklist at a Maximum Care Hospital - A Retrospective Analysis]. / Implementierung der perioperativen WHO-Sicherheitscheckliste an einem Klinikum der Maximalversorgung - eine retrospektive Analyse.

BACKGROUND: In recent years there has been a significant increase of surgical procedures worldwide. Perioperative complication occurred in approximately 10 %, mortality was about 0.5 %. Half of these adverse events were considered to have been preventable. With the introduction of a perioperative checklist by the WHO in 2008, a significant reduction of morbidity and mortality could be achieved. The aim of this study was to investigate the success of the implementation process of the checklist at a maximum care hospital over a three-year period and to expose and analyse any occurring issues. PATIENTS AND METHODS: At various time points (introduction phase, five months, one year and three years after implementation) a total of 358 operations was investigated. First the presence and the handling of the checklist were investigated followed by an analysis of possible influencing factors on the processing. To examine a potential perioperative malpractice, three typical perioperative errors known from the literature on patient safety were analysed. RESULTS: The presence of the checklist improved significantly during the study. With the exception of the first column (signed by ward nurse) the checklist was processed more often among the participants (anaesthesia nurse, anaesthesia physician, surgeon) over the time. However the "sign out" column edited by the surgeon at the end of the operation fell below expectations. In addition to the duration after implementation the level of experience of the surgeon was a relevant factor for a properly completed checklist. During the study a malpractice was found in two cases, a checklist could not be detected. CONCLUSION: Within the study we could demonstrate the difficulties of introducing a surgical checklist at a maximum care hospital. Therefore involved nursing or medical staff must be aware of the usefulness of the checklist and should be motivated to use it. In addition, periodical lectures, training courses and role modelling of nursing and medical staff are required. The objective must be to establish the checklist into daily routine as it is a simple and efficient tool to reduce perioperative morbidity and mortality.

The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

PURPOSE: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. METHODS: Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. RESULTS: Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. CONCLUSIONS: Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

Meloxicam, a COX-2 inhibitor, ameliorates ischemia/reperfusion injury in non-heart-beating donor livers.

BACKGROUND/AIMS: Chronic organ donor shortage has led to the consideration to expand the donor pool with livers from non-heart-beating donors (NHBD), although a higher risk of graft dys- or nonfunction is associated with these livers. We examined the effects of selective cyclooxygenase-2 (COX-2) inhibition on hepatic warm ischemia (WI) reperfusion (I/R) injury of NHBD. METHODS: Male Wistar rats were used as donors and meloxicam (5 mg/kg body weight) was administered into the preservation solution. Livers were excised after 60 min of WI in situ, flushed and preserved for 24 h at 4°C. Reperfusion was carried out in vitro at a constant flow for 45 min. During reperfusion (5, 15, 30 and 45 min), enzyme release of alanine aminotransferase and glutamate lactate dehydrogenase were measured as well as portal venous pressure, bile production and oxygen consumption. The production of malondialdehyde was quantified and TUNEL staining was performed. Quantitative PCR analyzed COX-2 mRNA. COX-2 immunohistochemistry and TxB(2) detection completed the measurements. RESULTS: Meloxicam treatment led to better functional recovery concerning liver enzyme release, vascular resistance and metabolic activity over time in all animals. Oxidative stress and apoptosis were considerably reduced. CONCLUSION: Cold storage using meloxicam resulted in significantly better integrity and function of livers retrieved from NHBD. Selective COX-2 inhibition is a new therapeutic approach achieving improved preservation of grafts from NHBD.

Anti-inflammatory role of glycine in reducing rodent postoperative inflammatory ileus.

BACKGROUND: Inflammatory events within the intestinal muscularis, including macrophage activation and leukocyte recruitment, have been demonstrated to participate in causing postoperative ileus. Recently, glycine has gained attention due to its beneficial immunomodulatory effects in transplantation, shock and sepsis. METHODS: Muscularis glycine receptors were investigated by immunohistochemistry. Gastrointestinal motility was assessed by in vivo transit distribution histograms with calculated geometric center analysis and jejunal circular smooth muscle contractility in a standard organ bath. The impact of glycine on the muscularis inflammatory responses to surgical manipulation of the intestine were measured by real-time PCR, nitric oxide Griess reaction, prostaglandin ELISA, Luminex and histochemistry. KEY RESULTS: Glycine-gated chloride channels were immunohistochemically localized to muscularis macrophages and postoperative infiltrating leukocytes. Preoperative glycine treatment significantly improved postoperative gastrointestinal transit and jejunal circular muscle contractility. Preoperative glycine injection significantly reduced the induction of interleukin-6 (IL-6), tumor necrosis factor-α, inducible nitric oxide synthase and intercellular adhesion molecule-1 mRNAs, which was associated with the attenuation in postoperative leukocyte recruitment. Nitric oxide and prostanoid release from the postsurgical inflamed muscularis was diminished by glycine. The secretion of the inflammatory proteins IL-6, monocyte chemotactic protein-1/chemokine ligand 2 and macrophage inflammatory protein-1α/chemokine ligand 3 were also significantly decreased by glycine pretreatment. CONCLUSIONS & INFERENCES: The data indicate that preoperative glycine reduces postoperative ileus via the early attenuation of primal inflammatory events within the surgically manipulated gut wall. Therapeutic modulation of resident macrophages by glycine is a potential novel pharmacological target for the prevention of postoperative ileus.

Influence of immunosuppression on alloresponse, inflammation and contractile function of graft after intestinal transplantation.

In small bowel transplantation (SBTx), graft manipulation, ischemia/reperfusion injury and acute rejection initiate a severe cellular and molecular inflammatory response in the muscularis propria leading to impaired motility of the graft. This study examined and compared the effect of tacrolimus and sirolimus on inflammation in graft muscularis. After allogeneic orthotopic SBTx, recipient rats were treated with tacrolimus or sirolimus. Tacrolimus and sirolimus attenuated neutrophilic, macrophage and T-cell infiltration in graft muscularis, which was associated with reduced apoptotic cell death. Nonspecific inflammatory mediators (IL-6, MCP-1) and T-cell activation markers (IL-2, IFN-gamma) were highly upregulated in allogeneic control graft muscularis 24 h and 7 days after SBTx, and tacrolimus and sirolimus significantly suppressed upregulation of these mediators. In vitro organ bath method demonstrated a severe decrease in graft smooth muscle contractility in allogeneic control (22% of normal control). Correlating with attenuated upregulation of iNOS, tacrolimus and sirolimus treatment significantly improved contractility (64% and 72%, respectively). Although sirolimus reduced cellular and molecular inflammatory response more efficiently after 24 h, contrary tacrolimus prevented acute rejection more efficiently. In conclusion, tacrolimus and sirolimus attenuate cellular and molecular inflammatory response in graft muscularis and subsequent dysmotility of the graft after allogeneic SBTx.

Role of interleukin 10 in murine postoperative ileus.

BACKGROUND AND AIMS: Intestinal manipulation triggers an inflammatory cascade within the muscularis causing postoperative ileus (POI). The aim of this study was to investigate the recovery and therapeutic potential of interleukin 10 (IL10) for POI. METHODS: POI was induced by bowel surgical manipulation (SM) in wild-type, IL10(-/-) and recombinant murine IL10 (rmIL10)-treated mice. Immunohistochemistry localised IL10 in the muscularis externa, histochemistry quantified neutrophil recruitment, and quantitative PCR quantified alterations in mRNA. Luminex multiplex analysis, Griess reaction and ELISA measured proteins, nitric oxide (NO) and prostanoid release from the muscularis externa, respectively, in 24 h organ culture. Gastrointestinal transit and jejunal circular muscle organ bath techniques assessed gastrointestinal function. RESULTS: In IL10 knockouts compared with the wild type, the expression of numerous proinflammatory mRNAs (IL6, IL1 beta, chemokine C-C motif ligand 2 (CCL2) and haem oxygenase-1) and proteins (IL6, IL1 alpha, IL12, IL17, interferon gamma, tumour necrosis factor alpha, CCL2, interferon-inducible protein-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were accentuated, and release of muscle inhibitors NO and prostanoids was increased; motility never recovered from manipulation and mortality rate was 87.5%. In wild types, complete functional recovery occurred in 7 days with no mortality. SM delay in transit and suppression in jejunal circular muscle contractions were significantly improved by rmIL10 treatment. Upregulation in IL1 beta, IL6 and CCL2 mRNAs and inflammatory mediators (IL1 alpha, IL6, CCL2, macrophage inflammatory protein-1 alpha, GM-CSF, NO and prostaglandin) after SM were significantly less with rmIL10 treatment, which resulted in a decrease in neutrophil recruitment compared with SM controls. CONCLUSION: IL10 plays an obligatory role in postoperative intestinal recovery, and exogenous IL10 prevents its development. Pre-emptive exogenous recombinant human IL10 could be a treatment for the prevention of clinical POI.

IL-10 administration attenuates pulmonary neutrophil infiltration and alters pulmonary iNOS activation following hemorrhagic shock.

OBJECTIVE AND DESIGN: Several studies report immuno-modulatory effects of endogenous IL-10 after trauma. This study investigates the effect of IL-10 administration on systemic and pulmonary inflammation in hemorrhagic shock. MATERIAL AND METHODS: Male C57/BL6 mice (4-6 animals per group) were subjected to volume controlled hemorrhagic shock for 3 hrs followed by resuscitation. Animals were either subcutaneously injected with 0.9 % saline (Shock group) or with recombinant mouse IL-10 (Shock+IL-10 group) 1 h before and 1 h after the induction of hemorrhagic shock. Serum TNF-alpha, IL-6, and keratinocyte (KC) concentrations were measured with the Luminex multiplexing platform. Acute pulmonary inflammation was assessed by pulmonary myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activity. RESULTS: IL-10 administration significantly decreased serum TNF-alpha (10.30 +/- 1.68 vs 37.42 +/- 10.64; p < 0.05), IL-6 (44.22 +/- 6.65 vs 85.24 +/- 7.94; p < 0.05), and KC (276.74 +/- 52.67 vs 465.61 +/- 58.98; p < 0.05) levels following hemorrhagic shock. Further, pulmonary MPO activity was significantly lower (2698.85 +/- 431.10 vs 4580.67 +/- 294.38; p < 0.05) and pulmonary iNOS activity upregulated. CONCLUSION: These findings suggest that administration of IL-10 modulates the degree of hemorrhage-induced systemic and pulmonary inflammation and support the notion of a central role for iNOS in acute lung injury.

Alvimopan and COX-2 inhibition reverse opioid and inflammatory components of postoperative ileus.

Our objective was to investigate the therapeutic potential of peripheral opioid antagonism with alvimopan and anti-inflammatory cyclooxygenase 2 (COX-2) inhibition in an animal model of postoperative ileus with pain management. Intestinal manipulation was conducted in mice and rats with or without postoperative morphine injection. Rodents were orally fed non-digestible fluorescein (FITC)-labelled dextran and transit measured after a period of 90 min. The immunomodulatory effects of morphine and alvimopan were determined on nitric oxide released from the organ cultured muscularis externa. Surgical manipulation of the intestine resulted in a delay in gastrointestinal transit after 24 h that worsened with exogenous morphine. Alvimopan did not significantly alter transit of control or manipulated animals, but significantly antagonized the transit delaying effects of morphine. However, when the inflammatory component was robust enough to obscure a further opioid induced delay in gastrointestinal transit, alvimopan ceased to be effective in improving postoperative intestinal function. Cyclooxygenase 2 inhibition significantly diminished the inflammatory component of postoperative ileus. Surgical manipulation resulted in an increased release of nitric oxide from the inflamed isolated muscularis externa in 24-h organ culture which was not altered by morphine or alvimopan. Two distinct mechanisms exist which participate in postoperative bowel dysfunction: a local inflammatory response which is antagonized by COX-2 inhibition, and a morphine-induced alteration in neural function which can be blocked with alvimopan.

Effects of a bradycardic agent on postischemic cardiac recovery in rabbits.

Decreasing heart rate might be beneficial for improvement of myocardial energetics and could reduce the severity of myocardial ischemia. We examined the contribution of heart rate reduction by cilobradine (DK-AH 269), a direct sinus node inhibitor, on left ventricular function and peripheral vasomotion in anesthetized rabbits with experimental myocardial infarction. The rabbits were randomized to receive either placebo (n=10) or cilobradine (n=7). Cilobradine decreased significantly heart rate from 163 +/- 33 to 131 +/- 13 bpm, p< 0.05, without any inotopic or vascular effects. After 60 min coronary occlusion and 30 min reperfusion, both systolic and diastolic ventricular function were more reduced in the cilobradine group; i.e. maximal left ventricular pressure significantly decreased to 62 +/- 11 mmHg, p < 0.05 (placebo: 77 +/- 9 mmHg); dP/dt(min) significantly decreased to -904 +/- 247 mmHg, p < 0.05 (placebo: -1106 +/- 242 mmHg). However, infarct size in the cilobradine group was significantly smaller compared with the placebo group. In conclusion, cilobradine reduced heart rate without any negative inotropic effect and reduced infarct size. On that account, this bradycardic agent might open a promising therapeutical avenue to treat postischemic dysfunction.