Posttransplant Diastolic Hypertension

Kirk, Allan D.; Jacobson, Laura; Heisey, Dennis M.; Fass, N.; Sollinger, Hans W.; Pirsch, John D.

doi:10.1097/00007890-199712270-00015

Cited by 45 publications

(5 citation statements)

References 11 publications

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“…The authors did not speculate on the mechanism of the tacrolimus overdose‐related myocardial ischemia. Tacrolimus increases endothelin release from vascular endothelium (8, 9). Endothelin causes arterial vasoconstriction (12).…”

Section: Discussionmentioning

confidence: 99%

“…However, one case report described myocardial ischemia following tacrolimus overdose in a bone marrow transplant recipient (7). Tacrolimus increases endothelin, a potent vasoconstrictor, release from the vascular endothelium (8, 9). These findings suggest that tacrolimus may cause hypertension, nephrotoxicity, and possibly myocardial ischemia through its potential vasoconstrictive activity.…”

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confidence: 99%

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Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

Takahashi

Sugimoto

Hishikawa

et al. 2005

Pediatric Transplantation

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Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18-22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 PM on day 6, and tacrolimus was discontinued at 9:00 PM; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

Takahashi

Sugimoto

Hishikawa

et al. 2005

Pediatric Transplantation

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“…[3][4][5][6][7] Posttransplantation diastolic hypertension has been attributed to TGF-␤ induction and resulting endothelinmediated renal arteriolar vasospasm and reninangiotensin pathway activation. 79 By reducing renal hypertension and systemic vasoconstriction, calcineurin-inhibitor-sparing regimens may be expected to decrease these risks as well as to improve long-term graft survival.…”

Section: Theoretical Benefitsmentioning

confidence: 99%

Strategies to Reduce Toxicities and Improve Outcomes in Renal Transplant Recipients

Alloway

2002

Pharmacotherapy

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Ongoing improvements in immunosuppression and posttransplantation care have dramatically improved patient and graft outcomes after transplantation. The frequency of graft loss due to acute rejection has declined considerably as a result of the availability of a variety of more potent immunosuppressive agents and probably also because of refined clinical care and follow-up. Complications of long-term administration of corticosteroids (steroids) and calcineurin inhibitors, however, have become increasingly apparent as patients live longer with their transplant, and attention is shifting to long-term issues. Use of both steroids and calcineurin inhibitors is associated with metabolic toxicities such as hypertension, hyperlipidemia, diabetes, bone loss, and cataracts. These contribute to posttransplantation morbidity and may negatively affect patient and allograft survival. A variety of troublesome cosmetic side effects, such as hirsutism, gingival hyperplasia, alopecia, obesity, and cushingoid appearance, also are associated with these drugs. These effects can detract from patient self-esteem and compliance with the immunosuppressive regimen. In the past 2 decades, the introduction of second-generation immunosuppressive drugs, such as tacrolimus, mycophenolate mofetil, sirolimus, and anti-interleukin-2 receptor monoclonal antibodies, has provided some alternatives to classic immunosuppressant choices. Patients experiencing undesirable adverse events now can be converted to another immunosuppressive regimen that ultimately will improve graft and patient survival rates and improve quality of life after transplantation.

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“…CsA is known to cause numerous unwanted side effects. It has been shown that CsA increases Ang II receptors independently from CaN inhibition, which causes vasoconstriction and systemic hypertension and can promote CH [ 35 , 45 – 47 ]. This may be due to CsA alleviating the cardioprotective action of CnA β .…”

Section: Discussionmentioning

confidence: 99%

Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II‐Induced Cardiomyocyte Hypertrophy by Modulating CnA‐NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells

Chen

Xing

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Previous studies have demonstrated that calcium-/calmodulin-dependent protein kinase II (CaMKII) and calcineurin A-nuclear factor of activated T-cell (CnA-NFAT) signaling pathways play key roles in cardiac hypertrophy (CH). However, the interaction between CaMKII and CnA-NFAT signaling remains unclear. H9c2 cells were cultured and treated with angiotensin II (Ang II) with or without silenced CaMKIIδ (siCaMKII) and cyclosporine A (CsA, a calcineurin inhibitor) and subsequently treated with Wenxin Keli (WXKL). Patch clamp recording was conducted to assess L-type Ca2+ current (ICa-L), and the expression of proteins involved in signaling pathways was measured by western blotting. Myocardial cytoskeletal protein and nuclear translocation of target proteins were assessed by immunofluorescence. The results indicated that siCaMKII suppressed Ang II-induced CH, as evidenced by reduced cell surface area and ICa-L. Notably, siCaMKII inhibited Ang II-induced activation of CnA and NFATc4 nuclear transfer. Inflammatory signaling was inhibited by siCaMKII and WXKL. Interestingly, CsA inhibited CnA-NFAT pathway expression but activated CaMKII signaling. In conclusion, siCaMKII may improve CH, possibly by blocking CnA-NFAT and MyD88 signaling, and WXKL has a similar effect. These data suggest that inhibiting CaMKII, but not CnA, may be a promising approach to attenuate CH and arrhythmia progression.

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Posttransplant Diastolic Hypertension

Abstract: These data support the hypothesis that posttransplant diastolic hypertension is a result of TGF-beta-induced, endothelin-mediated arteriolar vasoconstriction and subsequent activation of the renin-angiotensin pathway. These effects are independent of immune-mediated graft injury.

Cited by 45 publications

References 11 publications

Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

Strategies to Reduce Toxicities and Improve Outcomes in Renal Transplant Recipients

Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II‐Induced Cardiomyocyte Hypertrophy by Modulating CnA‐NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells

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