F. N. Gava

Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G-protein receptor kinase.

G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the activation of GRK2 was reduced. 1400W or GRK2 inhibitor reduced mortality, improved echocardiographic cardiac parameters, and prevented organ damage. Therefore, during sepsis, NOS2-derived NO increases GRK2, which leads to a reduction in β-adrenergic receptor density, contributing to the heart dysfunction. Isolated cardiac myocyte data indicate that NO acts through the soluble guanylyl cyclase/cGMP/PKG pathway. GRK2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction.NEW & NOTEWORTHY The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore, G protein-coupled receptor kinase isoform 2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction.

Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas’ hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease.Trypanosoma cruzi infection causes Chagas disease, but mechanisms underlying pathogenesis are unclear. Here, Silva et al. show that canonical PI3Kγ signaling in myeloid cells restricts T. cruzi infection in mice and that high PIK3CG expression correlates with low parasite levels in human Chagas’ hearts.

Tissue doppler evaluation in non-sedated rabbits during doxorubicin treatment

Seattle, Washington, June 12 – 15, 2013 Index of Abstracts POSTER PRESENTATIONS On Display: Thursday, June 13, 7:00 AM – 7:00 PM Friday, June 14, 7:00 AM – 7:30 PM Saturday, June 15, 7:00 AM – 2:30 PM Attended by ALL Authors Eligible for ACVIM Resident Research Awards: Thursday, June 13, 9:50 AM – 10:30 AM Friday, June 14, 9:50 AM – 10:30 AM Attended by ALL Authors – Wine & Cheese Reception: Friday, June 14, 6:00 PM – 7:30 PM # Presenting Auhor Abstract Title SMALL ANIMAL CARDIOLOGY C-22 Evandro Zacche TIME-DOMAIN HEART RATE VARIABILITY IN DOGS WITH SEPSIS C-23 Robert Sanders USE OF TRANSESOPHAGEAL ECG TO GUIDE PLACEMENT OF A TRANSESOPHAGEAL PACING CATHETER TO THE OPTIMAL PACING SITE C-24 Erin Trageser EVALUATION OF SERUM BIOMARKERS OF COLLAGEN TURNOVER IN CATS WITH HYPERTROPHIC CARDIOMYOPATHY C-25 Takuma Aoki VIBRATION EFFECT ON INTERSTITIAL CELLS OF THE CANINE MITRAL VALVE C-26 Emily Chapel EFFECTS OF CATHETER SHAPE, ELECTRODE SIZE AND INTERELECTRODE SPACING ON TRANSESOPHAGEAL ATRIAL PACING IN DOGS C-27 Craig Ruaux BIOLOGICAL VARIABILITY AND CRITICAL CHANGE VALUES FOR ULTRASENSITIVE CARDIAC TROPONIN-I AND NT-proBNP ARE LOWER IN DOGS WITH CARDIAC DISEASE THAN IN HEALTHY CONTROL DOGS C-28 Bryan Eason INFLUENCE OF BETA BLOCKERS ON SURVIVAL IN DOGS WITH SEVERE SUBAORTIC STENOSIS C-29 Aparecido Antonio COMPARATIVE STUDY OF ARTERIAL BLOOD PRESSURE OBTAINED BY Camacho DIFFERENT NON-INVASIVE METHODS IN NON-SEDATED NEW ZEALAND WHITE RABBITS C-30 Maria Reimann INFLUENCE OF R-R INTERVAL VARIATIONS ON THE DEGREE OF MITRAL REGURGITATION IN DOGS WITH MYXOMATOUS MITRAL VALVE DISEASE C-31 Philip Fox EVALUATION OF NT-PRO-BRAIN NATRIURETIC PEPTIDE (NT-proBNP) AS A PROGNOSTIC INDICATOR OF SHORT-TERM OUTCOME IN CATS WITH HEART FAILURE C-32 Jodi Sangster CARDIAC BIOMARKERS IN HYPERTHYROID CATS

Time-domain heart rate variability in dogs with sepsis

Seattle, Washington, June 12 – 15, 2013 Index of Abstracts POSTER PRESENTATIONS On Display: Thursday, June 13, 7:00 AM – 7:00 PM Friday, June 14, 7:00 AM – 7:30 PM Saturday, June 15, 7:00 AM – 2:30 PM Attended by ALL Authors Eligible for ACVIM Resident Research Awards: Thursday, June 13, 9:50 AM – 10:30 AM Friday, June 14, 9:50 AM – 10:30 AM Attended by ALL Authors – Wine & Cheese Reception: Friday, June 14, 6:00 PM – 7:30 PM # Presenting Auhor Abstract Title SMALL ANIMAL CARDIOLOGY C-22 Evandro Zacche TIME-DOMAIN HEART RATE VARIABILITY IN DOGS WITH SEPSIS C-23 Robert Sanders USE OF TRANSESOPHAGEAL ECG TO GUIDE PLACEMENT OF A TRANSESOPHAGEAL PACING CATHETER TO THE OPTIMAL PACING SITE C-24 Erin Trageser EVALUATION OF SERUM BIOMARKERS OF COLLAGEN TURNOVER IN CATS WITH HYPERTROPHIC CARDIOMYOPATHY C-25 Takuma Aoki VIBRATION EFFECT ON INTERSTITIAL CELLS OF THE CANINE MITRAL VALVE C-26 Emily Chapel EFFECTS OF CATHETER SHAPE, ELECTRODE SIZE AND INTERELECTRODE SPACING ON TRANSESOPHAGEAL ATRIAL PACING IN DOGS C-27 Craig Ruaux BIOLOGICAL VARIABILITY AND CRITICAL CHANGE VALUES FOR ULTRASENSITIVE CARDIAC TROPONIN-I AND NT-proBNP ARE LOWER IN DOGS WITH CARDIAC DISEASE THAN IN HEALTHY CONTROL DOGS C-28 Bryan Eason INFLUENCE OF BETA BLOCKERS ON SURVIVAL IN DOGS WITH SEVERE SUBAORTIC STENOSIS C-29 Aparecido Antonio COMPARATIVE STUDY OF ARTERIAL BLOOD PRESSURE OBTAINED BY Camacho DIFFERENT NON-INVASIVE METHODS IN NON-SEDATED NEW ZEALAND WHITE RABBITS C-30 Maria Reimann INFLUENCE OF R-R INTERVAL VARIATIONS ON THE DEGREE OF MITRAL REGURGITATION IN DOGS WITH MYXOMATOUS MITRAL VALVE DISEASE C-31 Philip Fox EVALUATION OF NT-PRO-BRAIN NATRIURETIC PEPTIDE (NT-proBNP) AS A PROGNOSTIC INDICATOR OF SHORT-TERM OUTCOME IN CATS WITH HEART FAILURE C-32 Jodi Sangster CARDIAC BIOMARKERS IN HYPERTHYROID CATS

Comparative study of arterial blood pressure obtained by different non-invasive methods in non-sedated new zealand white rabbits

Seattle, Washington, June 12 – 15, 2013 Index of Abstracts POSTER PRESENTATIONS On Display: Thursday, June 13, 7:00 AM – 7:00 PM Friday, June 14, 7:00 AM – 7:30 PM Saturday, June 15, 7:00 AM – 2:30 PM Attended by ALL Authors Eligible for ACVIM Resident Research Awards: Thursday, June 13, 9:50 AM – 10:30 AM Friday, June 14, 9:50 AM – 10:30 AM Attended by ALL Authors – Wine & Cheese Reception: Friday, June 14, 6:00 PM – 7:30 PM # Presenting Auhor Abstract Title SMALL ANIMAL CARDIOLOGY C-22 Evandro Zacche TIME-DOMAIN HEART RATE VARIABILITY IN DOGS WITH SEPSIS C-23 Robert Sanders USE OF TRANSESOPHAGEAL ECG TO GUIDE PLACEMENT OF A TRANSESOPHAGEAL PACING CATHETER TO THE OPTIMAL PACING SITE C-24 Erin Trageser EVALUATION OF SERUM BIOMARKERS OF COLLAGEN TURNOVER IN CATS WITH HYPERTROPHIC CARDIOMYOPATHY C-25 Takuma Aoki VIBRATION EFFECT ON INTERSTITIAL CELLS OF THE CANINE MITRAL VALVE C-26 Emily Chapel EFFECTS OF CATHETER SHAPE, ELECTRODE SIZE AND INTERELECTRODE SPACING ON TRANSESOPHAGEAL ATRIAL PACING IN DOGS C-27 Craig Ruaux BIOLOGICAL VARIABILITY AND CRITICAL CHANGE VALUES FOR ULTRASENSITIVE CARDIAC TROPONIN-I AND NT-proBNP ARE LOWER IN DOGS WITH CARDIAC DISEASE THAN IN HEALTHY CONTROL DOGS C-28 Bryan Eason INFLUENCE OF BETA BLOCKERS ON SURVIVAL IN DOGS WITH SEVERE SUBAORTIC STENOSIS C-29 Aparecido Antonio COMPARATIVE STUDY OF ARTERIAL BLOOD PRESSURE OBTAINED BY Camacho DIFFERENT NON-INVASIVE METHODS IN NON-SEDATED NEW ZEALAND WHITE RABBITS C-30 Maria Reimann INFLUENCE OF R-R INTERVAL VARIATIONS ON THE DEGREE OF MITRAL REGURGITATION IN DOGS WITH MYXOMATOUS MITRAL VALVE DISEASE C-31 Philip Fox EVALUATION OF NT-PRO-BRAIN NATRIURETIC PEPTIDE (NT-proBNP) AS A PROGNOSTIC INDICATOR OF SHORT-TERM OUTCOME IN CATS WITH HEART FAILURE C-32 Jodi Sangster CARDIAC BIOMARKERS IN HYPERTHYROID CATS

Ventilação mandatória intermitente sincronizada versus ventilação com suporte pressórico e volume garantido em coelhos induzidos à hemorragia aguda

The effects of synchronized intermittent mandatory ventilation (SIMV) versus volume assured pressure support ventilation (VAPSV) on cardiorespiratory parameters in propofol-anesthetized rabbits induced to acute hypovolemia were evaluated. Twenty New Zealand white rabbits were randomly allotted to: GM under SIMV and GV under VAPSV. In premedication, ketamine (15mg/kg) and xylazine (1mg/kg) were administered intramuscularly. Propofol was used to induce (8mg/kg) and to maintain anesthesia (0.5mg/kg/min). Following, according to each group, the ventilation mode was started. After thirty minutes of anesthesia induction, rabbits were induced to hypovolemia by removing 12ml/kg of arterial blood. The initial measurement of parameters (M0) was recorded thirty minutes after anesthesia induction. Additional recordings were performed at 10-minute intervals after hypovolemia induction (M1 to M6). Cardiac output (CO) was bigger in GM. In both groups, arterial pressures and central venous pressure (CVP) decreased from M1, while arterial partial pressure of oxygen (PaO2) increased from M4. The respiratory effort was greater in GV at all times studied. In conclusion, VAPSV and SIMV were safe for arterial oxygenation and provided adequate gas exchange. However, the SIMV is more appropriate for hypovolemic rabbits, because it maintains hemodynamic stability and promotes lower respiratory work.